Bone Resorption: Bone loss due to osteoclastic activity.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Bone Remodeling: The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.Root Resorption: Resorption in which cementum or dentin is lost from the root of a tooth owing to cementoclastic or osteoclastic activity in conditions such as trauma of occlusion or neoplasms. (Dorland, 27th ed)Bone Density: The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Bone Development: The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.Osteoprotegerin: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.Bone Neoplasms: Tumors or cancer located in bone tissue or specific BONES.Osteoblasts: Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.Diphosphonates: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.Osteogenesis: The process of bone formation. Histogenesis of bone including ossification.Alveolar Bone Loss: Resorption or wasting of the tooth-supporting bone (ALVEOLAR PROCESS) in the MAXILLA or MANDIBLE.Bone Diseases: Diseases of BONES.Receptor Activator of Nuclear Factor-kappa B: A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Fetal Resorption: The disintegration and assimilation of the dead FETUS in the UTERUS at any stage after the completion of organogenesis which, in humans, is after the 9th week of GESTATION. It does not include embryo resorption (see EMBRYO LOSS).Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium.Skull: The SKELETON of the HEAD including the FACIAL BONES and the bones enclosing the BRAIN.Cathepsin K: A cysteine protease that is highly expressed in OSTEOCLASTS and plays an essential role in BONE RESORPTION as a potent EXTRACELLULAR MATRIX-degrading enzyme.Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures; OSTEITIS; SPLENOMEGALY with infarct; ANEMIA; and extramedullary hemopoiesis (HEMATOPOIESIS, EXTRAMEDULLARY).Parathyroid Hormone: A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.Tooth Resorption: Resorption of calcified dental tissue, involving demineralization due to reversal of the cation exchange and lacunar resorption by osteoclasts. There are two types: external (as a result of tooth pathology) and internal (apparently initiated by a peculiar inflammatory hyperplasia of the pulp). (From Jablonski, Dictionary of Dentistry, 1992, p676)Bone Diseases, MetabolicFemur: The longest and largest bone of the skeleton, it is situated between the hip and the knee.Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX.Bone Regeneration: Renewal or repair of lost bone tissue. It excludes BONY CALLUS formed after BONE FRACTURES but not yet replaced by hard bone.Etidronic Acid: A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.Bone Density Conservation Agents: Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the FIBULA laterally, the TALUS distally, and the FEMUR proximally.Osteoporosis, Postmenopausal: Metabolic disorder associated with fractures of the femoral neck, vertebrae, and distal forearm. It occurs commonly in women within 15-20 years after menopause, and is caused by factors associated with menopause including estrogen deficiency.Bone Transplantation: The grafting of bone from a donor site to a recipient site.Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.X-Ray Microtomography: X-RAY COMPUTERIZED TOMOGRAPHY with resolution in the micrometer range.Osteocytes: Mature osteoblasts that have become embedded in the BONE MATRIX. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi.Hypercalcemia: Abnormally high level of calcium in the blood.Tooth Movement: Orthodontic techniques used to correct the malposition of a single tooth.Osteitis Deformans: A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Fractures, Bone: Breaks in bones.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.Parietal Bone: One of a pair of irregularly shaped quadrilateral bones situated between the FRONTAL BONE and OCCIPITAL BONE, which together form the sides of the CRANIUM.Ovariectomy: The surgical removal of one or both ovaries.Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth.Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Bone Marrow Transplantation: The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.Bone Substitutes: Synthetic or natural materials for the replacement of bones or bone tissue. They include hard tissue replacement polymers, natural coral, hydroxyapatite, beta-tricalcium phosphate, and various other biomaterials. The bone substitutes as inert materials can be incorporated into surrounding tissue or gradually replaced by original tissue.Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR).Ilium: The largest of three bones that make up each half of the pelvic girdle.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.Absorptiometry, Photon: A noninvasive method for assessing BODY COMPOSITION. It is based on the differential absorption of X-RAYS (or GAMMA RAYS) by different tissues such as bone, fat and other soft tissues. The source of (X-ray or gamma-ray) photon beam is generated either from radioisotopes such as GADOLINIUM 153, IODINE 125, or Americanium 241 which emit GAMMA RAYS in the appropriate range; or from an X-ray tube which produces X-RAYS in the desired range. It is primarily used for quantitating BONE MINERAL CONTENT, especially for the diagnosis of OSTEOPOROSIS, and also in measuring BONE MINERALIZATION.Clodronic Acid: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Periosteum: Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.Parathyroid Hormone-Related Protein: A ubiquitously expressed, secreted protein with bone resorption and renal calcium reabsorption activities that are similar to PARATHYROID HORMONE. It does not circulate in appreciable amounts in normal subjects, but rather exerts its biological actions locally. Overexpression of parathyroid hormone-related protein by tumor cells results in humoral calcemia of malignancy.Phosphorus: A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions.Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.Periodontitis: Inflammation and loss of connective tissues supporting or surrounding the teeth. This may involve any part of the PERIODONTIUM. Periodontitis is currently classified by disease progression (CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS) instead of age of onset. (From 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, American Academy of Periodontology)Mice, Inbred C57BLTooth Eruption: The emergence of a tooth from within its follicle in the ALVEOLAR PROCESS of the MAXILLA or MANDIBLE into the ORAL CAVITY. (Boucher's Clinical Dental Terminology, 4th ed)Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.TartratesMandible: The largest and strongest bone of the FACE constituting the lower jaw. It supports the lower teeth.Maxilla: One of a pair of irregularly shaped bones that form the upper jaw. A maxillary bone provides tooth sockets for the superior teeth, forms part of the ORBIT, and contains the MAXILLARY SINUS.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Vacuolar Proton-Translocating ATPases: Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.Periapical Granuloma: Chronic nonsuppurative inflammation of periapical tissue resulting from irritation following pulp disease or endodontic treatment.Maxillary DiseasesMinerals: Native, inorganic or fossilized organic substances having a definite chemical composition and formed by inorganic reactions. They may occur as individual crystals or may be disseminated in some other mineral or rock. (Grant & Hackh's Chemical Dictionary, 5th ed; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Tooth Root: The part of a tooth from the neck to the apex, embedded in the alveolar process and covered with cementum. A root may be single or divided into several branches, usually identified by their relative position, e.g., lingual root or buccal root. Single-rooted teeth include mandibular first and second premolars and the maxillary second premolar teeth. The maxillary first premolar has two roots in most cases. Maxillary molars have three roots. (Jablonski, Dictionary of Dentistry, 1992, p690)Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.Osteosclerosis: An abnormal hardening or increased density of bone tissue.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Tooth Apex: The tip or terminal end of the root of a tooth. (Jablonski, Dictionary of Dentistry, 1992, p62)Molar: The most posterior teeth on either side of the jaw, totaling eight in the deciduous dentition (2 on each side, upper and lower), and usually 12 in the permanent dentition (three on each side, upper and lower). They are grinding teeth, having large crowns and broad chewing surfaces. (Jablonski, Dictionary of Dentistry, 1992, p821)Calcium, Dietary: Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Incisor: Any of the eight frontal teeth (four maxillary and four mandibular) having a sharp incisal edge for cutting food and a single root, which occurs in man both as a deciduous and a permanent tooth. (Jablonski, Dictionary of Dentistry, 1992, p820)Porphyromonas gingivalis: A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium produces a cell-bound, oxygen-sensitive collagenase and is isolated from the human mouth.Periodontal Ligament: The fibrous CONNECTIVE TISSUE surrounding the TOOTH ROOT, separating it from and attaching it to the alveolar bone (ALVEOLAR PROCESS).NFATC Transcription Factors: A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Calcium Radioisotopes: Unstable isotopes of calcium that decay or disintegrate emitting radiation. Ca atoms with atomic weights 39, 41, 45, 47, 49, and 50 are radioactive calcium isotopes.Temporal Bone: Either of a pair of compound bones forming the lateral (left and right) surfaces and base of the skull which contains the organs of hearing. It is a large bone formed by the fusion of parts: the squamous (the flattened anterior-superior part), the tympanic (the curved anterior-inferior part), the mastoid (the irregular posterior portion), and the petrous (the part at the base of the skull).Receptors, Calcitonin: Cell surface proteins that bind calcitonin and trigger intracellular changes which influence the behavior of cells. Calcitonin receptors outside the nervous system mediate the role of calcitonin in calcium homeostasis. The role of calcitonin receptors in the brain is not well understood.Osteopontin: A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.Tooth Socket: A hollow part of the alveolar process of the MAXILLA or MANDIBLE where each tooth fits and is attached via the periodontal ligament.Lumbar Vertebrae: VERTEBRAE in the region of the lower BACK below the THORACIC VERTEBRAE and above the SACRAL VERTEBRAE.Dental Cementum: The bonelike rigid connective tissue covering the root of a tooth from the cementoenamel junction to the apex and lining the apex of the root canal, also assisting in tooth support by serving as attachment structures for the periodontal ligament. (Jablonski, Dictionary of Dentistry, 1992)Spine: The spinal or vertebral column.Radius: The outer shorter of the two bones of the FOREARM, lying parallel to the ULNA and partially revolving around it.Tooth Exfoliation: Physiologic loss of the primary dentition. (Zwemer, Boucher's Clinical Dental Terminology, 4th ed)Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Microradiography: Production of a radiographic image of a small or very thin object on fine-grained photographic film under conditions which permit subsequent microscopic examination or enlargement of the radiograph at linear magnifications of up to several hundred and with a resolution approaching the resolving power of the photographic emulsion (about 1000 lines per millimeter).Teriparatide: A polypeptide that consists of the 1-34 amino-acid fragment of human PARATHYROID HORMONE, the biologically active N-terminal region. The acetate form is given by intravenous infusion in the differential diagnosis of HYPOPARATHYROIDISM and PSEUDOHYPOPARATHYROIDISM. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)Bacteroidaceae Infections: Infections with bacteria of the family BACTEROIDACEAE.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Mandibular DiseasesGlycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.Multiple Myeloma: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.Integrin-Binding Sialoprotein: A highly glycosylated and sulfated phosphoprotein that is found almost exclusively in mineralized connective tissues. It is an extracellular matrix protein that binds to hydroxyapatite through polyglutamic acid sequences and mediates cell attachment through an RGD sequence.Dentin: The hard portion of the tooth surrounding the pulp, covered by enamel on the crown and cementum on the root, which is harder and denser than bone but softer than enamel, and is thus readily abraded when left unprotected. (From Jablonski, Dictionary of Dentistry, 1992)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Periodontium: The structures surrounding and supporting the tooth. Periodontium includes the gum (GINGIVA), the alveolar bone (ALVEOLAR PROCESS), the DENTAL CEMENTUM, and the PERIODONTAL LIGAMENT.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Ulna: The inner and longer bone of the FOREARM.Foot Bones: The TARSAL BONES; METATARSAL BONES; and PHALANGES OF TOES. The tarsal bones consists of seven bones: CALCANEUS; TALUS; cuboid; navicular; internal; middle; and external cuneiform bones. The five metatarsal bones are numbered one through five, running medial to lateral. There are 14 phalanges in each foot, the great toe has two while the other toes have three each.Microscopy, Electron, Scanning: Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Hydroxycholecalciferols: Hydroxy analogs of vitamin D 3; (CHOLECALCIFEROL); including CALCIFEDIOL; CALCITRIOL; and 24,25-DIHYDROXYVITAMIN D 3.Polymethyl Methacrylate: Polymerized methyl methacrylate monomers which are used as sheets, moulding, extrusion powders, surface coating resins, emulsion polymers, fibers, inks, and films (From International Labor Organization, 1983). This material is also used in tooth implants, bone cements, and hard corneal contact lenses.Bicuspid: One of the eight permanent teeth, two on either side in each jaw, between the canines (CUSPID) and the molars (MOLAR), serving for grinding and crushing food. The upper have two cusps (bicuspid) but the lower have one to three. (Jablonski, Dictionary of Dentistry, 1992, p822)Humerus: Bone in humans and primates extending from the SHOULDER JOINT to the ELBOW JOINT.Femur Neck: The constricted portion of the thigh bone between the femur head and the trochanters.Polyethylenes: Synthetic thermoplastics that are tough, flexible, inert, and resistant to chemicals and electrical current. They are often used as biocompatible materials for prostheses and implants.Mice, Inbred ICRGingiva: Oral tissue surrounding and attached to TEETH.Periapical Periodontitis: Inflammation of the PERIAPICAL TISSUE. It includes general, unspecified, or acute nonsuppurative inflammation. Chronic nonsuppurative inflammation is PERIAPICAL GRANULOMA. Suppurative inflammation is PERIAPICAL ABSCESS.Renal Osteodystrophy: Decalcification of bone or abnormal bone development due to chronic KIDNEY DISEASES, in which 1,25-DIHYDROXYVITAMIN D3 synthesis by the kidneys is impaired, leading to reduced negative feedback on PARATHYROID HORMONE. The resulting SECONDARY HYPERPARATHYROIDISM eventually leads to bone disorders.Bone Cysts: Benign unilocular lytic areas in the proximal end of a long bone with well defined and narrow endosteal margins. The cysts contain fluid and the cyst walls may contain some giant cells. Bone cysts usually occur in males between the ages 3-15 years.Biomechanical Phenomena: The properties, processes, and behavior of biological systems under the action of mechanical forces.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Parathyroid Glands: Two pairs of small oval-shaped glands located in the front and the base of the NECK and adjacent to the two lobes of THYROID GLAND. They secrete PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Giant Cell Tumor of Bone: A bone tumor composed of cellular spindle-cell stroma containing scattered multinucleated giant cells resembling osteoclasts. The tumors range from benign to frankly malignant lesions. The tumor occurs most frequently in an end of a long tubular bone in young adults. (From Dorland, 27th ed; Stedman, 25th ed)Postmenopause: The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Prosthesis Failure: Malfunction of implantation shunts, valves, etc., and prosthesis loosening, migration, and breaking.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Vitamin D: A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Methylmethacrylates: The methyl esters of methacrylic acid that polymerize easily and are used as tissue cements, dental materials, and absorbent for biological substances.Radiography, Panoramic: Extraoral body-section radiography depicting an entire maxilla, or both maxilla and mandible, on a single film.Dental Sac: Dense fibrous layer formed from mesodermal tissue that surrounds the epithelial enamel organ. The cells eventually migrate to the external surface of the newly formed root dentin and give rise to the cementoblasts that deposit cementum on the developing root, fibroblasts of the developing periodontal ligament, and osteoblasts of the developing alveolar bone.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Receptors, Vitronectin: Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Interleukin-6: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.Cholecalciferol: Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Titanium: A dark-gray, metallic element of widespread distribution but occurring in small amounts; atomic number, 22; atomic weight, 47.90; symbol, Ti; specific gravity, 4.5; used for fixation of fractures. (Dorland, 28th ed)Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Osteolysis, Essential: Syndromes of bone destruction where the cause is not obvious such as neoplasia, infection, or trauma. The destruction follows various patterns: massive (Gorham disease), multicentric (HAJDU-CHENEY SYNDROME), or carpal/tarsal.Tooth Extraction: The surgical removal of a tooth. (Dorland, 28th ed)Orthodontics, Corrective: The phase of orthodontics concerned with the correction of malocclusion with proper appliances and prevention of its sequelae (Jablonski's Illus. Dictionary of Dentistry).Tooth, Deciduous: The teeth of the first dentition, which are shed and replaced by the permanent teeth.Stress, Mechanical: A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.Diaphyses: The shaft of long bones.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Bone Morphogenetic Protein 6: A bone morphogenetic protein that is a potent inducer of BONE formation. It plays additional roles in regulating CELL DIFFERENTIATION of non-osteoblastic cell types and epithelial-mesenchymal interactions.Phosphates: Inorganic salts of phosphoric acid.Tooth Mobility: Horizontal and, to a lesser degree, axial movement of a tooth in response to normal forces, as in occlusion. It refers also to the movability of a tooth resulting from loss of all or a portion of its attachment and supportive apparatus, as seen in periodontitis, occlusal trauma, and periodontosis. (From Jablonski, Dictionary of Dentistry, 1992, p507 & Boucher's Clinical Dental Terminology, 4th ed, p313)Culture Media, Conditioned: Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).Jaw, Edentulous: The total absence of teeth from either the mandible or the maxilla, but not both. Total absence of teeth from both is MOUTH, EDENTULOUS. Partial absence of teeth in either is JAW, EDENTULOUS, PARTIALLY.Hyperparathyroidism: A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES.Hypocalcemia: Reduction of the blood calcium below normal. Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm. (Dorland, 27th ed)Cell Line: Established cell cultures that have the potential to propagate indefinitely.Estrogens: Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.

Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice. (1/2466)

Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and then indirectly to increase differentiation and function of osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are resistant to collagenase cleavage of type I collagen. Human PTH(1-34) was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days. Osteoclast numbers, the size of the bone marrow spaces and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal. The r/r mice were not resistant to other skeletal effects of PTH because abundant interstitial collagenase mRNA was detected in the calvarial periosteum of PTH-treated, but not vehicle-treated, r/r and +/+ mice. Calcemic responses, 0.5-10 hours after intraperitoneal injection of PTH, were blunted in r/r mice versus +/+ mice. Thus, collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption.  (+info)

The development and structure of the chimpanzee mandible. (2/2466)

The sites of growth and remodeling, and the associated changes in cortical bone structure, have been studied in the chimpanzee mandible and compared with those previously reported in the human and macaque mandibles. The location of the principal sites of growth, and the distribution of the areas of deposition and resorption in the ramus, were found to be similar in all three species. In the chimpanzee, unlike Man, the bone being deposited at the condyle, posterior border of the ramus and coronoid process was plexiform in nature, indicating very rapid growth. The pattern of remodeling in the mandibular body, on the other hand, showed marked species differences at the chin and on the submandibular lingual surface, which account for the contrasts seen in the adult morphology of these regions. Although the pattern of distribution of cortical densities differed from that of surface remodeling, the information they give is complementary in analysing bone growth. The densest regions were found to coincide with sites of consistent lamellar deposition, while the least dense regions were those where plexiform bone was formed. Areas where remodeling led to the greatest reorientation of bone tissue within the cortex showed the greatest disparity between the two patterns.  (+info)

Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease. (3/2466)

We determined the effects of the potent bisphosphonate ibandronate in a murine model of human myeloma bone disease. In this model, bone lesions typical of the human disease develop in mice following inoculation of myeloma cells via the tail vein. Treatment with ibandronate (4 micrograms per mouse per day) significantly reduced the occurrence of osteolytic bone lesions in myeloma-bearing mice. However, ibandronate did not prevent the mice from developing hindlimb paralysis and did not produce a detectable effect on survival. There was no significant effect of ibandronate on total myeloma cell burden, as assessed by morphometric measurements of myeloma cells in the bone marrow, liver, and spleen, or by measurement of serum IgG2b levels. These results support clinical findings that bisphosphonates may be useful for the treatment of myeloma-associated bone destruction, but suggest that other therapies are also required to reduce tumor growth.  (+info)

Study of the effect of lactational bone loss on blood lead concentrations in humans. (4/2466)

Lactation and other clinical states of high bone turnover have been suggested to release lead (Pb) stored in bone into blood and tissues. Previous observations on the influences of lactation have been anecdotal, or at high blood Pb concentrations with varying past exposures, or complicated by postpartum fluid changes. A prospective observational study was performed to investigate possible changes in blood lead concentrations at multiple intervals during lactation for 6 months postpartum and to relate changes in blood lead concentrations to changes in bone density and other variables. Volunteer pregnant subjects (n = 58) were enrolled from a midwifery service at an academic public health hospital. Subjects were mostly Hispanic, recently immigrated, of low economic status, not receiving supplemental calcium, and had low blood Pb concentrations (2.35 +/- 2.05 microg/dl at enrollment). Bone density losses over 6 months for the group averaged -2.46 +/- 6.33% at the vertebral spine and -0.67 +/- 5.21% at the femoral neck. In predicting final bone density, apart from initial bone density only the total number of breast-feedings was a significant independent variable of the variables tested, accounting for an additional 12% of the variability. No changes in blood Pb concentrations were seen over the interval beyond 2 weeks postpartum (minimum detectable change was 0.4 microg/dl). There was no relation between the changes in bone density and changes in blood Pb or the integrated blood Pb over the 2-week to 6-month period. Normal (nonlactating) bone resorption rates contribute a large fraction of the Pb in blood during low-exposure circumstances. However, during lactation the increase in bone resorptive processes is probably relatively small with a larger decrease in deposition accounting for net bone loss, as suggested by other investigations. Thus, concomitant release of Pb from bones of lactating subjects with low blood lead concentrations on this background of high normal resorption was not large enough for detection.  (+info)

Biochemical markers of bone turnover in breast cancer patients with bone metastases: a preliminary report. (5/2466)

BACKGROUND: Some biochemical markers of bone turnover are expected to reflect the disease activity of metastatic bone tumor. In the present study six biochemical markers were evaluated to determine appropriate markers for the detection of metastatic bone tumors from breast cancer (BC). METHODS: A panel of bone turnover markers was assessed in 11 normocalcemic patients with bone metastases from BC and in 19 BC patients without clinical evidence of bone metastases. Bone formation was investigated by measuring serum bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and carboxy-terminal propeptide of type I procollagen (PICP): Bone resorption was investigated by measuring serum carboxy-terminal telopeptide of type I collagen (ICTP), fasting urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr). RESULTS: PICP was influenced by age and menopausal status. Significant correlations were observed between each of bone turnover markers except between BALP and OC. The mean levels of the six bone turnover markers were higher in patients with bone metastases than in those without them and significance was observed except for OC. The best diagnostic efficiency by receiver-operating characteristic (ROC) analysis was provided by ICTP followed by Pyr or D-Pyr, BALP, PICP and OC and significance was observed between ICTP and OC. Multiple logistic regression analysis adjusted by age revealed that the only significant marker related to bone metastases was ICTP. CONCLUSIONS: Serum ICTP appears to be the leading marker of bone metastases from BC. However, to reveal the clinical usefulness of these markers, further examination will be needed to account for the ease and cost-effectiveness of the measurements.  (+info)

Acute fasting diminishes the circadian rhythm of biochemical markers of bone resorption. (6/2466)

OBJECTIVE: Biochemical markers of bone turnover exhibit circadian rhythms with the peak during the night/early morning and the nadir in the late afternoon. The nocturnal increase in bone resorption could theoretically be caused by the absence of food consumption which brings about a decrease in net calcium absorption and an increase in parathyroid hormone (PTH), followed by increased bone resorption in response to the body's demand for calcium. The aim of the present study was to assess the influence of a 33-h fast on the circadian variation in biochemical markers of bone turnover. DESIGN: Eleven healthy premenopausal women (age: 24+/-5 years) participated in a randomised, cross-over study consisting of two periods: either 33h of fasting (fasting) followed 1 week later by a 33-h period with regular meals eaten at 0800-0830h, 1130-1230h and 1800-1900h (control) or vice versa. METHODS: Urinary CrossLaps (U-CL/Cr) corrected with creatinine, as a marker of bone resorption; serum osteocalcin (sOC) as a marker of bone formation; serum intact PTH (iPTH); serum phosphate; and serum calcium corrected with albumin. RESULTS: Both the fasting and the control periods showed a significant circadian rhythm in U-CL/Cr (P<0.001), but the decrease was significantly less pronounced in the morning hours during the fasting period. Fasting resulted in a significant decrease in serum iPTH (throughout the study period) as compared with the control period (P<0.05-0.001). No change was observed in sOC by fasting. CONCLUSION: Food consumption has a small influence on the circadian variation in bone resorption, independent of PTH. The fall in iPTH during fasting may be secondary to an increased bone resorption produced by fasting.  (+info)

A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. (7/2466)

Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n = 22), or oral calcium 1 g twice daily for 12 months (n = 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P < 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.  (+info)

An odyssey from breast to bone: multi-step control of mammary metastases and osteolysis by matrix metalloproteinases. (8/2466)

Development of metastases distant to the primary site of solid tumors marks late stages of tumor progression. Almost all malignant mammary tumors are carcinomas arising from the breast epithelium, but the morphological and molecular alterations in the mammary stroma surrounding the premalignant and the growing tumor contribute to its conversion into neoplastic tissue. Two parameters are critical for initiation of the metastatic process and access of tumor cells to the circulation. These are the ability of tumor cells to invade the basement membrane and the stroma, and the neovascularization of breast tumor tissue. A major site for development of distant metastases is the skeleton. After colonizing the bone, tumor cells promote a cascade of events leading to recruitment of osteoclasts and subsequent osteolytic bone destruction. A ubiquitous theme of neoplastic progression of breast tumors is the overproduction of matrix metalloproteinases. In this review, we summarize the recent insights into the functional consequences of matrix metalloproteinase expression and activation during malignant conversion in the breast, and after bone colonization. The current literature supports the hypothesis that matrix metalloproteinases play a key role in the metastatic expansion of most, if not all, mammary tumors and in the ensuing bone loss.  (+info)

Definition of osteoclast-activating factor in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is osteoclast-activating factor? Meaning of osteoclast-activating factor as a finance term. What does osteoclast-activating factor mean in finance?
Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ...
A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO4) and zirconium dioxide (ZrO2) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA
It is generally accepted that bone formation is depressed during corticosteroid treatment, but the effects of glucocorticoids on bone resorption are less well characterized. We have investigated the effects of short-term treatment with high-dose oral glucocorticoids on biochemical markers of bone turnover in 20 consecutive patients with asthma who sought help for acute respiratory obstruction in our emergency department. Serum concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP), reflecting bone resorption, and the carboxy-terminal propeptide of type 1 procollagen (P1CP), reflecting bone formation, were measured by radioimmunoassay. Changes of the circulating levels of the bone resorption marker 1CTP after treatment were age dependent with a significant negative correlation (r = -0.54, P = 0.01). The dependency on age remained when correcting, in a multiple linear regression analysis, for 1CTP levels at admission, weight, sex, and daily maintenance dose of ...
Do you have a protocol for osteoclast resorption on dentine slices? I have done a literature search (1966-present) and the seminal article seems to be Boyde & Jones (1984) Resorption of dentine by isolated osteoclasts in vitro. Br Dent J 156:216-220. Help! Our provencial library doesnt have this journal. Donna Montague, M.S. Research Associate Physiology/Biophysics and Orthopaedic Surgery University of Arkansas for Medical Sciences (501) 603-1239 ...
Author: Rumpler, M. et al.; Genre: Meeting Abstract; Published in Print: 2011-05-07; Title: Microcracks and osteoclast resorption activity in vitro
The three main mechanisms by which osteoporosis develops are an inadequate peak bone mass (the skeleton develops insufficient mass and strength during growth), excessive bone resorption and inadequate formation of new bone during remodeling. An interplay of these three mechanisms underlies the development of fragile bone tissue.[9] Hormonal factors strongly determine the rate of bone resorption; lack of estrogen (e.g. as a result of menopause) increases bone resorption as well as decreasing the deposition of new bone that normally takes place in weight-bearing bones. The amount of estrogen needed to suppress this process is lower than that normally needed to stimulate the uterus and breast gland. The α-form of the estrogen receptor appears to be the most important in regulating bone turnover. In addition to estrogen, calcium metabolism plays a significant role in bone turnover, and deficiency of calcium and vitamin D leads to impaired bone deposition; in addition, the parathyroid glands react ...
Monocytes are frequently found adjacent to active bone resorption surfaces in both physiological and pathological situations and may play a key role in bone resorption. There is strong circumstantial...
Mechanisms of bone invasion by squamous carcinomas of the head and neck have been investigated using fresh tumours and established tumour cell lines in an in vitro bone resorption assay with 45Ca-labelled mouse calvaria. Fresh tumours regularly resorb bone in vitro. Activity is consistently reduced by indomethacin. The tumours release E 2 prostaglandins (PGE 2) in amounts sufficient to account for ~50% of the bone resorption observed. Small amounts of non-prostaglandin (indomethacin-resistant) osteolytic factors are also produced. Control non-neoplastic tissues show a variable capacity to resorb bone in vitro; PGE 2 levels in these tissues may be related to their content of inflammatory cells. Tumour cell lines also resorb bone in vitro but, for most lines, activity is not significantly blocked by indomethacin and PGE 2 levels are generally insufficient to account for the osteolysis observed. Non-prostaglandin bone resorbing factors thus predominate. It is concluded that most squamous cancers of ...
Bone, despite its rigid nature, is not a permanent, immutable tissue. It is in fact a very dynamic and living tissue that maintains its structure via an equilibrium of opposing activities: Bone Regeneration and Bone Resorption. Both activities are constantly ongoing in living bone. This process of bone regeneration and bone resorption in equilibrium is…
Bone reabsorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These are the cells responsible for the resorption of bone. Osteoclasts are generally present on the outer layer of bone, just beneath the periosteum. Attachment of the osteoclast to the osteon begins the process. The osteoclast then induces an infolding of its cell membrane and secretes collagenase and other enzymes important in the resorption process. High levels of calcium, magnesium, phosphate and products of collagen will be released into the extracellular fluid as the osteoclasts tunnel into the mineralized bone. Osteoclasts are prominent in the tissue destruction found in psoriatic arthritis and rheumatology disorders. The human body is in a constant state of bone remodeling. Bone ...
To clarify what kind of process participates in bone resorption, time course of indices of bone resorption was investigated using 13-day-old embryonic chick calvaria. When calvariae were cultured...
The invention relates to a combined pharmaceutical preparation comprising parathyroid hormone and a bone resorption inhibitor, said preparation being adapted for (a) the administration of parathyroid hormone during a period of approximately 6 to 24 months; (b) after the administration of parathyroid hormone has been terminated, the administration of a bone resorption inhibitor during a period of approximately 12 to 36 months.
The invention relates to a combined pharmaceutical preparation comprising parathyroid hormone and a bone resorption inhibitor, said preparation being adapted for (a) the administration of parathyroid hormone during a period of approximately 6 to 24 months; (b) after the administration of parathyroid hormone has been terminated, the administration of a bone resorption inhibitor during a period of approximately 12 to 36 months.
Increased bone turnover may be a risk factor for fracture [Lønning 2005]. However, it is uncertain whether markers of bone resorption and markers of bone formation are both associated with fracture risk [Looker 2000]. Therefore, we will measure bone formation and bone resorption markers at baseline, year 1 and year 5. Blood specimens will be shipped to and stored in a central laboratory for future assays of bone biomarkers. For markers of bone formation, the N-terminal Propeptide of Type I Collagen (PINP) will be measured. For bone resorption markers, serum levels of cross-linked N-telopeptides of type I collagen (NTx) will be measured. Note: Subjects must fast 12-14 hours prior to blood draw ...
Osteoporosis (OP) is a common chronic skeletal disorder in aging individuals. In-spite of the progress made in this market, there is still a great demand for safer and more specific drugs for extended administration. Excessive bone resorption by osteoclasts is central to the pathogenesis of OP and other bone-related diseases. Thus, inhibition of osteoclast activity is a desired outcome in the treatment of bone and bone-related disorders. However, complete irreversible shutdown of resorption by current drugs and uncontrolled duration of activity increase the risk for hypocalcemia, atypical fractures and osteonecrosis of the jaw limiting their utilization and decreasing patients compliance to their administration.. The combined expression of M-CSF receptor c-FMS and αvβ3 integrin is unique to osteoclasts. Moreover, signaling through these receptors is essential to organize the osteoclast cytoskeleton elements and for its resorption machinery. Studies in animal models demonstrated that ...
Also Known As: Bone Losses, Osteoclastic; Bone Resorptions; Loss, Osteoclastic Bone; Losses, Osteoclastic Bone; Osteoclastic Bone Losses Show All ,, ...
The tyrosine kinase inhibitor TAS-115 that blocks VEGF receptor and hepatocyte growth factor receptor MET signaling exhibits antitumor properties in xenografts of human gastric carcinoma. In this study, we have evaluated the efficacy of TAS-115 in preventing prostate cancer metastasis to the bone and bone destruction using the PC3 cell line. When PC3 cells were injected into proximal tibiae in nude mouse, severe trabecular and cortical bone destruction and subsequent tumor growths were detected. Oral administration of TAS-115 almost completely inhibited both PC3-induced bone loss and PC3 cell proliferation by suppressing osteoclastic bone resorption. In an ex vivo bone organ culture, PC3 cells induced osteoclastic bone resorption when co-cultured with calvarial bone, but TAS-115 effectively suppressed the PC3-induced bone destruction. We found that macrophage colony-stimulating factor-dependent macrophage differentiation and subsequent receptor activator of NF-κB ligand-induced osteoclast formation
Extracted from text ... SA Pharmaceutical Journal - April 2006 40 DRUG INFO Protos(r) - The first of a new class for osteoporosis: dual action bone agent Approved indication Protos(r) contains strontium ranelate and is indicated for the treatment of postmenopausal osteoporosis to reduce the risk of vertebral and peripheral fractures, including the hip. Mode of action Strontium ranelate has a unique pharmacological profile characterised by an inhibition of bone resorption and a simultaneous stimulation of bone formation. It targets the bone remodelling process by stimulating osteoblast-mediated bone formation and by inhibiting osteoclast-mediated bone resorption. The dual mode of action of strontium ranelate may ..
Osteoporosis is a common disorder which affects up to 30% women and 12% men at some point in life. This mostly age-associated disorder has becoming increasingly a major clinical and public health issue as human lifespan increases. Osteoporosis is characterized by reduced bone mass, alterations in bone micro-architecture, reduced bone strength, and elevated risk of fracture (Kanis, 1994). Although both genetic and environmental factors influence the risk of osteoporosis, it has been shown that familial traits are one of the most important clinical risk factors, suggesting the role of genetic factors. The fundamental pathogenic mechanism underlying this disorder includes, (a) failure to achieve peak bone mass during growth and development, (b) excessive bone resorption, and (c) defects in bone formation. Gene knockouts in mice have demonstrated that transcription factors Runx2 and a downstream factor Osterix (Osx) are essential for osteoblast differentiation and bone formation during development. However,
Illustration showing bone resorption; osteoclasts are breaking down bone and releasing minerals, to transfer calcium from the bone fluid into the blood. - Stock Image C024/9603
0055] Any amount of a pharmaceutical composition can be administered to a subject. The dosages will depend on many factors including the mode of administration and the age of the subject. In younger people there is extensive bone-turnover due to growing bone. Typically, the amount of a compound or agent of the present invention (e.g., 4-P-PDOT, a derivative, analog, conjugate or prodrug of 4-P-PDOT; a pharmaceutical acceptable salt thereof) contained within a single dose will be an amount that effectively prevent, delay or correct bone resorption in a subject in need thereof without inducing significant toxicity. As used herein the term "therapeutically effective amount" is meant to refer to an amount effective to achieve the desired therapeutic effect. A therapeutically effective amount is also one in which any adverse side effects of the compound are outweighed by the therapeutically beneficial effects. Typically, a compound or agent of the present invention (e.g., 4-P-PDOT, a derivative, ...
Principal Investigator:KITAZAWA Riko, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Experimental pathology
Principal Investigator:SHIBUTANI Toshiaki, Project Period (FY):1997 - 1998, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Conservative dentistry
Clodronate, Disodium Salt - CAS 88416-50-6 - Calbiochem CAS 88416-50-6 A non-amino, chloro-containing bisphosphonate that acts as a potent inhibitor of osteoclast-mediated bone resorption. - Find MSDS or SDS, a COA, data sheets and more information.
Biochemical markers of bone turnover reflect bone formation or bone resorption. These markers (both formation and resorption) may be elevated in high-bone-turnover states (eg, early postmenopausal ost... more
Type 2 diabetes mellitus (T2DM) is the most common type of diabetes mellitus. It accounts for more than 90% of diabetic patients and usually develops after 35-40 years of age. T2DM is characterized by hyperglycemia and redundant fatty acid secretion due to insulin resistance and decreased insulin sensitivity (Schwartz, 2016). Diabetic osteoporosis is a major complication of T2DM that originates mainly from alterations in the bone microenvironment (Zhang et al., 2016), thus leading to subsequent bone loss, mineral density reduction and fractures (Schwartz, 2016).. High glucose (HG) and free fatty acids (FFA) reportedly inhibit osteogenic differentiation (You et al., 2014) and induce apoptosis of osteoblasts (Feng et al., 2011). Bone metabolic homeostasis relies on the balance between osteoblast-induced bone formation and osteoclast-induced bone resorption (Raisz, 2005). Diabetic osteoporosis primarily results from the disequilibrium between osteoblast and osteoclast, as osteoblast activity is ...
The pattern of changes in serum PTH, combined with the pattern of elevation in biochemical markers of bone remodeling (increases in bone formation markers followed by increases in bone resorption markers), suggests a pathway through which daily PTH injection may temporarily uncouple bone ...
Questions and answers about tooth root bone resorption Teeth gums roots and bone can resorb for a number of reasons or causes Learn how the diagnosis process starts what can be done to stop cure or prevent it suggested treatments More dental questions, dentist practices, Learn new fix treat repair replace options.
Buy fosamax generic - paypal. Active alendronate ingredient - non-hormonal specific inhibitor of an osteoclastic bone resorption, suppresses osteoclasts
Introduction: Inflammation is a critical hallmark of autoimmune arthritis (AA) and cancer. We have previously shown that the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. We have identified IL-17, a critical pro-inflammatory cytokine involved in osteoclastic bone resorption in AA as the underlying mechanism for increased metastasis. In addition, high levels of cyclooxygenase 2 (COX-2) is linked to both AA and breast cancer metastasis. We report that blocking the IL-17 and COX-2 pathways simultaneously significantly reduces the development of breast cancer associated metastasis in a spontaneous model of AA.. Methods: 4T1 mammary gland tumors were generated in mice genetically prone to develop AA (designated SKG mice). When tumors reached , 0.2 gms, anti-IL17 antibody treatment was injected intraperitoneally once a week for three weeks. Celecoxib, a specific ...
1 The collection of new therapeutic entities first launched in 2003 originated from the following sources (a) CIPSLINE, Prous database (b) Iddb, Current Drugs database (c) IMS R& D Focus (d) Adis Business Intelligence R& D Insight (e) Pharmaprojects. 2 A. I. Graul, Drug News Perspect., 2004, 17, 43. 3 C. Boyer-Joubert, E. Lorthiois and F. Moreau, Ann. Rep. Med. Chem., 2003, 38, 347. 4 P. Bernardelli, B. Gaudilliere and F. Vergne, Ann. Rep. Med. Chem., 2002, 37, 257. 5 B. Gaudilliere, P..... ...
Nedwin, G E.; Mohler, M A.; and Luben, R A., "Cloning of the coding sequences of a human lymphokine, osteoclast-activating factor. Abstr." (1982). Subject Strain Bibliography 1982. 3923 ...
Affiliation:埼玉医大,医学部,助教授, Research Field:Orthopaedic surgery,Hematology, Keywords:OCIF,ODF,巨核球,転写制御,破骨細胞分化因子,骨吸収,bone resorption,活性型ビタミンD_3,proplatelet_formation,胞体突起形成(prpplatelet formation, PPF), # of Research Projects:2, # of Research Products:3
Regulation of RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. Osteoclasts are multinucleated cells that play a crucial role in bone resorption. In this study, we investigated the effects of N-methylpyrrolidone (NMP) on the regulation of RANKL-induced osteoclastogenesis. NMP inhibited RANKL-induced tartrate-resistant acid phosphatase activity and the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. The RANKL-induced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) and c-Fos, which are key transcription factors for osteoclastogenesis, was also reduced by treatment with NMP. Furthermore, NMP induced disruption of the actin rings and decreased the mRNAs of cathepsin K and MMP-9 (matrix metalloproteinase-9), both involved in bone resorption. Taken together, these results suggest that NMP inhibits osteoclast differentiation and ...
Bone is composed of a living protein framework upon which mineral crystals are placed. As bone breaks down, bits of this living protein framework appear in the urine. Tests of bone breakdown, called bone resorption tests, measure the amount of one specific bone protein in the urine (or in the blood) and thus gauge the current rate of bone breakdown. Urinary markers of bone breakdown (known as markers of bone resorption) are simple urine tests that can help determine if you are currently losing bone or not. Such bone breakdown testing can also indicate if your bone-building program is effective at reducing and normalizing the bone breakdown process.. As bone is broken down certain bone protein by-products are excreted in the urine. Measurement of the amount of these bone breakdown by-products can determine the rate of bone breakdown. A high rate of bone breakdown is strongly suggestive of current, ongoing bone loss and a greater risk for osteoporotic fracture. A low rate of bone resorption would ...
|i|Background.|/i| Sublesional osteoporosis (SLOP) is characterized by excessive bone resorption at the hip and knee region after spinal cord injury (SCI), resu...
New research in animals triggered by a combination of serendipity and counterintuitive thinking could point the way to treating fractures caused by rapid bone loss in people, including patients with metastatic cancers.. A series of studies at the University of North Carolina School of Medicine found that steroid drugs, known for inducing bone loss with prolonged use, actually help suppress a molecule thats key to the rapid bone loss process. A report of the new findings appears online Feb. 5, 2013 in the journal PLOS ONE.. Osteoporosis or the loss of bone mass is a major public health problem in the Western world and commonly results in hip and spine fractures. "But rib fractures are the most common and yet most unreported osteoporotic fractures and also occur in many cancers such as breast cancer, malignant melanoma, and myelomas, that metastasize and spread to the ribs," says Arjun Deb, MD, assistant professor in the departments of Medicine and Cell Biology and Physiology at UNC.. "While ...
Material and methods/results The authors used organ cultured neonatal mouse calvarial bones and isolated periosteal osteoblasts which express TLRs to study the role of TLR2 in bone resorption. LPS from the perio-pathogenic bacterium Porphyromonas gingivalis (Pg; which is a weak agonist for TLR4 but a strong for TLR2 because of the contaminating lipoprotein), enhanced number of osteoclasts, 45Ca release and bone matrix degradation (CTX) by a process inhibited by osteoprotegerin and zolendronic acid. LPS Pg enhanced the expression of osteoclastic genes (c-Fos, trap, oscar and cathepsin K) and reduced the expression of osteoblastic genes (osteocalcin, runx2, alp and procollagen α1). The effects were associated with increased mRNA and protein expression of RANKL, whereas OPG mRNA and protein were unaffected. Similar to LPS Pg, Pam2CSK4 (synthetic ligand for TLR2/TLR6), Pam3CSK4 (ligand for TLR1/TLR2), HKLM (a heat killed preparation of Listeria monocytogenes, a TLR2 agonist) and FSL1 (a synthetic ...
Fingerprint Dive into the research topics of Growth hormone protects against ovariectomy-induced bone loss in states of low circulating Insulin-like Growth Factor (IGF-1). Together they form a unique fingerprint. ...
Pharmacological Action:. Raloxifene : Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibtion of their proliferative capacity. This inhibition is thought to contribute to the drugs effect on bone resorption. Other mechanisms include the ...
The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. Either bone resorption is excessive, or bone formation is diminished. Bone matrix is manufactured by the osteoblast cells, whereas bone resorption is accomplished by osteoclast cells. Trabecular bone is the sponge-like bone in the center of long bones and vertabrae. Cortical bone is the hard outer shell of bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Long before any overt fractures occur, the small spicules of trabecular bone break and are reformed in the process known as remodeling. Bone will grow and change shape in response to physical stress. The bony prominences and attachments in runners are different in shape and size than those in weightlifters. It is an accumulation of fractures in trabecular bone that are incompletely repaired that leads to the manifestation of ...
Pathological bone resorption by osteoclasts is primarily treated with bisphosphonates. Because the administration of bisphosphonates is associated with a risk for multiple adverse symptoms, a precise understanding of the mechanisms underlying osteoclastogenesis is required to develop drugs with minimal side-effects. Osteoclastogenesis depends on receptor activator of nuclear factor kappa B (RANK) signaling mediated by TRAF6. We previously identified a highly conserved domain in the cytoplasmic tail of RANK (HCR), which did not share any significant homology with other proteins and was essential for osteoclastogenesis. HCR acts as a platform for the formation of Gab2- and Vav3-containing signal complexes, and ectopic expression of the HCR peptide inhibits osteoclastogenesis. Here, we uncover the mechanisms of HCR peptide-mediated inhibition of osteoclastogenesis. Expression of either the amino- or carboxyl-terminal half of the HCR peptide (N- or C-peptide) independently inhibited RANK signaling ...
The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the ...
p38 mitogen-activated protein kinase (MAPK), which is constitutively activated in human myeloma, has been implicated in bone destruction by this cancer, but the processes it recruits are obscure. In this study, we show that p38 activity in myeloma inhibits osteoblast differentiation and bone formation, but also enhances osteoclast maturation and bone resorption. p38 regulated the expression and secretion of the Wnt pathway antagonist DKK-1 and the monocyte chemoattractant MCP-1. Attenuating p38, DKK-1, or MCP-1 were each sufficient to reduce bone lesions in vivo. Although it is well known that DKK-1 inhibits osteoblast differentiation, we found that together with MCP-1, it could also promote osteoclast differentiation and bone resorption. The latter effects were mediated by enhancing expression of RANK in osteoclast progenitor cells and by upregulating secretion of its ligand RANKL from stromal cells and mature osteoblasts. In summary, our study defined the mechanisms by which p38 signaling in ...
Background: Hypothyroidism is associated with dysfunction of the bone turnover with reduced osteoblastic bone formation and osteoclastic bone resorption. Mesenchymal stem cells (MSCs) secrete various factors and cytokines that may stimulate bone regeneration.  The aim of this study was to determine the effects of MSCs-conditioned medium (CM) in hypothyroidism male ...
To determine whether 1,25-dihydroxyvitamin D (1,25(OH)2 D) can exert an anti-osteoporosis role through anti-aging mechanisms, we analyzed the bone phenotype of mice with 1,25(OH)2 D deficiency due to deletion of the enzyme, 25-hydroxyvitamin D 1α-hydroxylase, while on a rescue diet. 1,25(OH)2 D deficiency accelerated age-related bone loss by activating the p16/p19 senescence signaling pathway, inhibiting osteoblastic bone formation, and stimulating osteoclastic bone resorption, osteocyte senescence, and senescence-associated secretory phenotype (SASP). Supplementation of exogenous 1,25(OH)2 D3 corrected the osteoporotic phenotype caused by 1,25(OH)2 D deficiency or natural aging by inhibiting the p16/p19 pathway. The proliferation, osteogenic differentiation, and ectopic bone formation of bone marrow mesenchymal stem cells derived from mice with genetically induced deficiency of the vitamin D receptor (VDR) were significantly reduced by mechanisms including increased oxidative stress, DNA ...
Periodontitis is a common disease that is characterized by resorption of the alveolar bone and mediated by commensal bacteria that trigger host immune responses and bone destruction through unidentified mechanisms. We report that Nod1, an innate intracellular host receptor for bacterial peptidoglycan-related molecules, is critical for commensal-induced periodontitis in a mouse model. Mice lacking Nod1 exhibit reduced bone resorption as well as impaired recruitment of neutrophils to gingival tissues and osteoclasts to the alveolar bone, which mediate tissue and bone destruction. Further analysis showed that accumulation of a Nod1-stimulating commensal bacterium, NI1060, at gingival sites was sufficient to induce neutrophil recruitment and bone resorption. Genomic sequencing revealed that NI1060 is a mouse-specific bacterium that is related to bacteria associated with the development of aggressive periodontitis in humans. These findings provide insight into commensal-host interactions contributing ...
They display a characteristic ruffled border where proteases and acid are secreted, allowing for bone resorption and formation of resorption pits in the bone surface [25]. Osteoclast morphology varies between mammals and teleosts (bony fishes), and also between different groups of teleosts [20]. In the skeleton of young zebrafish for example, osteoclast activity is carried out by both mononucleated and multinucleated cells [26]. In fact, there is an ontogenetic progression from mono- towards multinucleated osteoclasts. In juvenile zebrafish, bone resorbing cells in the developing lower jaw are. at first mononucleated. In thin skeletal tissues such as the neural arch, mononucleated cells are even predominant in adults [26]. In rainbow trout, scale resorption Selleck BIBF1120 PD0325901 is predominantly carried out by mononucleated osteoclasts [27]. Although in mammals these mononucleated cells are often just regarded as osteoclast precursors, in fish mononucleated osteoclasts are active bone ...
Osteoclasts are large, multinucleated cells whose primary function is bone resorption. This process is regulated at multiple levels, including the proliferation and homing of osteoclast progenitors and their fusion into multinucleated cells (reviewed by Teitelbaum, 2000). Upon identification of appropriate resorption sites, osteoclasts reorganize their small matrix adhesions - podosomes - into a circular adhesion structure at the cell periphery known as the `sealing zone, and secrete protons and lysosomal enzymes into the space between the cell and the bone surface (Nesbitt and Horton, 1997; Salo et al., 1997). These structures form readily on bone surfaces; similar organization of podosome super-structures was observed in cells grown on standard tissue culture surfaces (Calle et al., 2004; Lakkakorpi et al., 1993; Zambonin-Zallone et al., 1988).. Podosomes are small (∼1 μm in diameter) dot-like adhesion structures found in osteoclasts, macrophages, dendritic cells and several types of ...
Background: Artificial hip joint replacement has undergone tremendous development in the past 100 years. In the beginning, complications, such as infection and early loosening, were the rule rather than the exception. Today, complications of any sort are rare during the first decade after the operation. Artificial hip joint replacement has been chosen as the "Operation of the Century" and has dramatically improved the quality of life of millions of patients. Unfortunately, in the long-term, prosthesis loosening due to pathological bone resorption (osteolysis) around the prosthesis is still common. Traditionally, the prosthesis is anchored in the bone with bone cement (Plexiglas). However, since this cementation method was suspected to cause late loosening, alternative methods, such as the implantation of so-called uncemented prostheses, have been developed and are being increasingly applied. Because the early movement of a prosthesis (migration) increases the risk of loosening, uncemented cups ...
Just minutes after I had asked her, Sherlock sent me the full study…a blog reader did the same just a few hours later…then another blogging friend…so now I have three copies of the same study…fabulous! Thank you all!. Lets dive right into the report, which is only six pages long but is packed with interesting information. There is so much good stuff, in fact, that it was difficult not to go ahead and print the whole thing! (I cannot do that, of course, for obvious reasons…) It begins with a description of MGUS and how it differs from multiple myeloma, including this item of interest, which explains why the bone turnover marker is so important, even in MGUS: Although MGUS is largely considered a benign condition, a number of studies show that patients with MGUS are at increased risk of developing fractures even before progression to myeloma. Elevated bone turnover is an independent predictor of fracture risk, and a number of studies have shown elevated bone resorption and/or reduced ...
Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions; the osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells, which give rise to osteoblasts, is very recent ...
Introduction. Aromatase inhibitors (AI) have become the accepted adjuvant therapy for postmenopausal patients with breast cancer with hormonal receptor expression1. AI brought about a marked reduction in estrogen levels through inhibition of the aromatase enzyme2 whose activity is relegated to peripheral tissues during menopause3. The American Society for Clinical Oncology (ASCO) recommends using the AI for 5 years, or for 2 or 3 years, after previous therapy with tamoxifen (TMX)4, where the latter option is prescribed for pre/peri-menopausal women5.. However, reduced estrogen levels increase bone resorption and raise the risk of fracture that occurs after menopause1,6-9. Clinical guidelines for the management of bone loss associated with AI (AIBL: Aromatase Inhibitor associated Bone Loss) recommends a strict monitoring of bone mineral density (BMD) and other risk factors to assess the need for treatment with anti-resortive therapies10.. Despite existing data, most of which based on randomized ...
Bone is living, growing tissue. It is made mostly of collagen, a protein that provides a soft framework, and calcium phosphate, a mineral that adds strength and hardens the framework.. This combination of collagen and calcium makes bone both flexible and strong, which in turn helps it to withstand stress. More than 99 percent of the bodys calcium is contained in the bones and teeth. The remaining 1 percent is found in the blood.. Throughout your lifetime, old bone is removed (resorption) and new bone is added to the skeleton (formation). During childhood and teenage years, new bone is added faster than old bone is removed. As a result, bones become larger, heavier, and denser. Bone formation outpaces resorption until peak bone mass (maximum bone density and strength) is reached around age 30. After that time, bone resorption slowly begins to exceed bone formation.. For women, bone loss is fastest in the first few years after menopause, and it continues into the postmenopausal years. ...
Alendronate is a bisphosphonate which prevent the osteoclast mediated bone resorption. Alendronate may decrease bone resorption and increase the density of the bone.
A. Gallois, J. Lachuer, G. Yvert, A. Wierinckx, F. Brunet, C. Rabourdin-Combe, C. Delprat, P. Jurdic, and M. Mazzorana (2010) J Bone Miner Res, 25(3):661-72.. ...
Root Resorption: Resorption in which cementum or dentin is lost from the root of a tooth owing to cementoclastic or osteoclastic activity in conditions such as trauma of occlusion or neoplasms. (Dorland, 27th ed)
The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways activated by RANK and immune receptors, whose ligands are expressed on the surface of osteoblasts. Signaling from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast ...
The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways activated by RANK and immune receptors, whose ligands are expressed on the surface of osteoblasts. Signaling from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast ...
The current standard of care for bone metastasis is therapies targeting the cells that degrade bone. These cells are directed by cancer cells to degrade bone in order to release pro-tumorigenic growth factors stored within the skeletal extracellular matrix. These therapies are not curative and do not halt metastasis-mediated bone degradation, indicating additional factors contribute to bone degradation. My research program focuses on the skeletal mechanical environment and its regulation of cancer. Specifically, I will investigate 1) the skeletons mechanical environment and its regulation of the remodeling process, and 2) the role of osteoblastic cells, which comprise the principal sensor and effector cells of mechanical cues, in metastatic processes. My long-term goal is to identify novel therapeutic targets for treating and preventing bone metastases as well as cancer-associated reductions in bone strength. My experimental approach uses novel in vivo and in vitro mechanical loading model ...
Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to
Osteoporosis is a public health problem that affects approximately 25 million people in the United States. Regardless of the etiology, osteoporosis is character...
541-737-2141. [email protected] The college is fully accredited by the American Veterinary Medical Association, Council on Education (COE).. ...
cdc15 encodes a member of the PCH protein family, conserved from yeast to mammals, that has been linked to actin cytoskeletal functions (Lippincott and Li, 2000). Though Cdc15p is the founding member of this protein family, little progress has been made toward understanding its precise function in cytokinesis. Here we have provided the first clues as to its critical role in this process. Cdc15p interacts directly with both the Arp2/3 complex activation machinery and the formin Cdc12p to orchestrate early events in CAR formation. As predicted by these interactions, the CAR does not form in the absence of Cdc15p function.. The critical role of Cdc15p in CAR formation was suggested by the observation that overexpression of Cdc15p was sufficient to drive medial recruitment of actin during interphase (Fankhauser et al., 1995). We have extended this observation to show that Cdc15p recruits Myo1p and other F-actin nucleators (this study; unpublished data) that presumably allow this to occur. Plo1p ...
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Mice whose bones cant respond to insulin develop high blood sugar and insulin resistance, both hallmarks of diabetes. Those symptoms are tied to a drop in osteocalcin. The findings suggest that osteocalcin, or perhaps a drug that targets bone, might hold promise in fighting the global epidemic of type 2 diabetes, according to the researchers.. Our study reveals a key molecular link between bone remodeling and metabolism, said Gerard Karsenty of Columbia University.. Bone is an organ that has to pay attention to where calories are going, added Thomas Clemens of Johns Hopkins University School of Medicine. It talks to muscle, fat, the pancreas. Its a player in energy metabolism.. And perhaps that makes a lot of sense, Karsenty said. The remodeling of bone relies on two cell types, bone-building osteoblasts and bone-resorbing osteoclasts, making bone the only organ with a cell type that is entirely focused on destroying host tissue. On a daily basis, the formation of bone is expensive in ...
Healthy bone maintains a balance of bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Many disease states, including chronic p...
    Background & aim: Long-term usage of inhaled corticosteroids is associated with osteoporosis in asthma patients. The purpose of this study was to determine the effect of long-term aerobic exercise on C-type collagen type T-terminal (CTX) as an indicator of bone resorption and serum calcium levels in asthmatic patients ...
This is a two-site, three-arm, open-label, pilot randomized controlled trial of bone anti-resorptive therapy during ART initiation in HIV-infected adults. Thirty (30) treatment-naïve HIV-infected adults initiating eligible first-line ART regimens will be randomized in a 1:1:1 fashion to one of the following three arms:. ...
Although the precise cause of osteoporosis is unknown, the process by which bone becomes porous is well known. Bone remodeling is controlled by a variety of hormones and inflammatory cytokines. When the body is exposed to inflammatory toxins, bone breakdown is overtaking bone buildup or bone resorption takes place at a faster speed than bone making. Both processes could lead to bone loss and osteoporosis ...
Bone, Tyrosine, Cell, Mice, Bone Formation, Gene, Bone Resorption, Cells, Osteoclast, Osteoclasts, Phosphorylation, Exon, Femur, Transgenic Mice, Growth, Transfer, Phosphotyrosine, Affect, Drive, Femurs
Purpose of Review The term osteopetrosis refers to a group of rare skeletal diseases sharing the hallmark of a generalized increase in bone density owing to a defect in bone resorption. Osteopetrosis...
Resorption of teeth happens when parts of a tooth begin to break down and are absorbed by your body. Injury, teeth grinding, and cavities can all cause this potentially painful condition. See your dentist for treatment since there are several dental procedure that may help save your tooth.
Medicine Leukotrienes play an role in inflammation and its sequelae: pain, swelling, bone resorption. their history, structure, synthesis, metabolism, biological effects, inhibitors, antagonists, and their role in pathogenesis of pulpal and periapical disease.
Lafantaisie-Favreau, C.-H., Guzmán-Morales, J., Sun, J., Chen, G., Harris, A., Smith, T. D., ... Hoemann, C. D. (2013). Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition. BMC Musculoskeletal Disorders, 14. ...
FIG 12.1 (A) Bony contours in a normal sagittal view of the maxillary and mandibular arches. (B) The initial resorption of bone in the lower arch destroys the lateral aspect of the lower ridge. (C) Further loss in the lower arch leaves the remaining bone in a more lateral position than the maxillary arch. Lateral resorption…
he levels of pERK had been considerably greater in WT than KO kidneys. All of the above modifications were most evident on day 2, one with the three examined
TY - JOUR. T1 - Mineral trioxide aggregate inhibits osteoclastic bone resorption. AU - Hashiguchi, D.. AU - Fukushima, H.. AU - Yasuda, H.. AU - Masuda, W.. AU - Tomikawa, M.. AU - Morikawa, K.. AU - Maki, K.. AU - Jimi, E.. PY - 2011/7/1. Y1 - 2011/7/1. N2 - Mineral trioxide aggregate (MTA), a commonly used endodontic repair material, is useful for both basic and clinical research, and the effect of MTA on osteoblast differentiation has been well-defined. However, the effects of MTA on osteoclastic bone resorption are not fully understood. Hence, the aim of this study is to examine the effect of MTA solution in the regulation of osteoclast bone-resorbing activity using osteoclasts formed in co-cultures of primary osteoblasts and bone marrow cells. MTA solution dosedependently reduced the total area of pits formed by osteoclasts. The reduction of resorption induced by 20% MTA treatment was due to inhibition of osteoclastic bone-resorbing activity and had no effect on osteoclast number. A 20% MTA ...
TY - JOUR. T1 - Evidence for an autocrine/paracrine role for interleukin-6 in bone resorption by giant cells from giant cell tumors of bone. AU - Ohsaki, Y.. AU - Takahashi, S.. AU - Scarcez, T.. AU - Demulder, A.. AU - Nishihara, T.. AU - Williams, R.. AU - Roodman, G. D.. PY - 1992/11. Y1 - 1992/11. N2 - Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (106/ml) contained large amounts of IL-6 (37.9 ± 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 ± 11.5 ng/ ml). Giant cells and stromal cells from giant cell tumors expressed IL- 6 mRNA, as indicated by polymerase chain reaction analysis and in situ ...
Excessive osteoclast formation and bone resorption are key causes of osteoporosis. Natural compounds can serve as alternative therapeutic agents for the prevention and treatment of osteoporosis, and some natural compounds may have advantages over traditional drugs. Here, we report that the natural compound gambogic acid (GBA), which is bioavailable, effective, and less toxic, inhibits osteoclast formation, thereby attenuating osteoclastic bone resorption in vitro . Further in vivo studies demonstrated that GBA prevented ovariectomy(OVX)-induced bone loss in a dose-dependent manner. Moreover, we demonstrated that GBA suppressed RANKL-induced JNK, p38 and AKT phosphorylation. Taken together, our results demonstrate that GBA inhibits osteoclast formation in vitro and in vivo , suggesting that it is of potential value in the treatment of osteoclast-related diseases. ...
Methods A strong and specific association between autoantibodies against citrullinated proteins and serum markers for osteoclast-mediated bone resorption was found in the serum of RA patients. Moreover, human osteoclasts expressed enzymes eliciting protein citrullination such as PAD2 and revealed specific inducible N-terminal citrullination of vimentin during their differentiation process. Affinity purified human autoantibodies against mutated citrullinated vimentin (MCV) not only bound to the osteoclast surface, but also lead to a robust induction of osteoclastogenesis and bone resorptive activity. Adoptive transfer of human MCV antibodies into RAG1-/- mice was followed by induction of osteopenia and increased osteoclastogenesis in vivo. This effect was based on the inducible release of TNFa from osteoclast precursors and the subsequent increase of CD11b+ osteoclast precursor cell numbers with enhanced expression of RANK and CSF1 receptors in vivo.. ...
TY - JOUR. T1 - Clinical usefulness of bisphosphonates in oncology. T2 - Treatment of bone metastases, antitumoral activity and effect on bone resorption markers. AU - Verì, A.. AU - DAndrea, M. R.. AU - Bonginelli, P.. AU - Gasparini, Giampietro. PY - 2007/1. Y1 - 2007/1. N2 - The present article overviews the role of bisphosphonates for the treatment and prevention of bone metastases and their antiangiogenic effects and antitumoral activity. The skeleton is a frequent and clinically relevant site of metastasis in cancer patients. The major events related to bone metastases include bone pain, bone loss, hypercalcemia, spinal cord compression, and fractures. On the basis of their radiographic features, bone metastases are classified as osteoblastic, osteoclastic, or mixed. The primary goals of treatment of bone metastases are reduction of the risk of pathological fractures and other skeletal-related events, and pain control. Bisphosphonates are used to prevent pathological fractures by ...
Human osteoclast formation from monocyte precursors under the action of receptor activator of nuclear factor-{kappa}B ligand (RANKL) was suppressed by granulocyte macrophage colony-stimulating factor (GM-CSF), with down-regulation of critical osteoclast-related nuclear factors. GM-CSF in the presence of RANKL and macrophage colony-stimulating factor resulted in mononuclear cells that were negative for tartrate-resistant acid phosphatase (TRAP) and negative for bone resorption. CD1a, a dendritic cell marker, was expressed in GM-CSF, RANKL, and macrophage colony-stimulating factor-treated cells and absent in osteoclasts. Microarray showed that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), was profoundly repressed by GM-CSF. Addition of MCP-1 reversed GM-CSF suppression of osteoclast formation, recovering the bone resorption phenotype. MCP-1 and chemokine RANTES (regulated on activation normal T cell expressed and secreted) permitted formation of TRAP-positive multinuclear cells in the ...
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. IMO iPSCs were generated from a patient carrying a homozygous c.11279G|A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing human TCIRG1. Embryoid bodies were generated and differentiated into monocytes. Non-adherent cells were harvested and further differentiated into osteoclasts on bovine bone slices. Release of the bone resorption biomarker CTX-I into the media of gene-corrected osteoclasts was 5-fold higher than that of the uncorrected osteoclasts and 35% of that of control osteoclasts. Bone resorption potential was confirmed by the presence of pits on the bones cultured with gene-corrected osteoclasts, absent in the uncorrected IMO osteoclasts. The disease phenotype was partially corrected in vitro, providing a valuable resource for therapy development for
BACKGROUND: Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohns disease (CD) although as yet the exact mechanisms have not been fully elucidated. AIM: To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. METHODS: Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients and pre- and post-treatment CD patients sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. RESULTS: There was a significant increase in bone formation markers osteocalcin (P | 0.05) and procollagen type 1 N-terminal propeptide (P | 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption
IL-1 is a proinflammatory cytokine that acts as an important mediator of the peripheral immune response during infection and inflammation (33). It is also known that IL-1 can induce bone destruction in a variety of diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease (34, 35). IL-1 stimulates osteoclast differentiation, fusion, and activation (35). In this paper, we examined the direct effect of IL-1 on osteoclast precursors which led to the elucidation of a previously unknown mechanism of downstream signaling pathways during IL-1-induced osteoclastogenesis.. Although TNF-α and IL-1 can activate early signaling pathways including NF-κB, JNK, and p38, which are important for RANKL-induced osteoclast differentiation, TNF-α alone has been shown to induce osteoclast differentiation in vitro (21, 36). IL-1 activates mature osteoclasts, thereby enhancing bone resorption (35), but our data along with previous studies (35, 36) demonstrate that IL-1 alone is insufficient to ...
Bone quality encompasses a number of bone tissue properties that govern mechanical resistance, such as bone geometry, cortical properties, trabecular microarchitecture, bone tissue mineralization, quality of collagen and bone apatite crystal, and presence of microcracks. All these properties are dependent on bone turnover and its variations. In populations, the decreases in bone resorption markers achieved with resorption inhibitors may predict in part the decrease in fracture risk. At the spine, however, this correlation exists down to a 40% fall in bone resorption markers; larger drops did not provide further protection against fractures in patients taking risedronate in one evaluation of this relationship. Osteoporosis medications can exert favorable effects on bone size and cortical thickness[Increase in bone size is an increase in height in some bones]. Such effects have been documented with teriparatide (PTH 1-34), which is the unique purely anabolic treatment for osteoporosis available to ...
BACKGROUND: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly
A protein analysis using a mass spectrometry indicated that there are serum proteins showing significant quantitative changes after the administration of infliximab. Among them, connective tissue growth factor (CTGF) seems to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, this study was conducted to investigate how CTGF is associated with the disease progression of RA. Serum samples were collected from RA patients in active or inactive disease stages, and before or after treatments with infliximab. CTGF production was evaluated by ELISA, RT-PCR, indirect immunofluorescence microscopy, and immunoblotting. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, a bone resorption assay and osteoclasts specific catalytic enzymes productions. The serum concentrations of CTGF in RA were greater than in normal healthy controls and disease controls. Interestingly, those were significantly higher in active RA patients compared to inactive RA patients.
Pharmacologic Profile of Risedronate Like all bisphosphonates, risedronate selectively adsorbs to active bone remodeling sites, where it acts to inhibit osteoclast-mediated bone resorption. Risedronate reduces the risk of fracture by preventing bone loss.10 This action results in increased BMD at fracture-prone skeletal sites, notably the lumbar spine and hip, in postmenopausal women with osteopenia11 or osteoporosis.12,13 It has the same effect in patients initiating14 or receiving15 high-dose, longterm ( 6 months) glucocorticoid therapy (prednisone 7.5 mg/d or equivalent). Pharmacokinetic Properties The pharmacokinetic characteristics of risedronate are summarized in Table 3.8,16-19 Risedronate is absorbed rapidly after oral administration and exhibits linear pharmacokinetics over the oral single-dose range of 5 mg to 30 mg.20 The extent of risedronate absorption is comparable when the dose is taken 30 minutes before breakfast or 2 hours after the evening meal, which may permit dosing ...
Osteolytic bone metastases are frequent in patients with advanced cancer of the breast, lung, and (to a lesser extent) the prostate. Roentgenography, bone scintigraphy, and bone biopsies are commonly used for the early identification and follow-up of these conditions. These methods have though marked shortcomings as they are all static methods giving a picture of the current situation in bone but not telling about rate of changes taking place in bone. Metabolic bone markers have been shown to be a useful tool for monitoring metastatic bone activity.. It has been shown that there are two different pathways of bone resorption: the cathepsin K-mediated pathway, which is active during physiological resorption of bone, and the matrix metalloproteinase pathway, which functions mainly in pathological situations. ICTP specifically reflects matrix metalloproteinase-mediated pathological degradation of bone collagen (1, 2). ICTP is thus a highly specific marker of bone degradation in bone metastasis and ...
Our study shows that TREM-2-deficient individuals have a striking defect in OC development, which results in impaired bone resorption in vitro. TREM-2-deficient OC precursors fail to fuse into multinucleated cells, do not develop extensive rearrangements of actin cytoskeleton, and show reduced or no expression of typical OC markers such as vitronectin and calcitonin receptors. TREM-2-deficient immature OCs do express TRAP; however, this molecule is also expressed in other bone marrow-derived cells. This block in OC development leads to impaired performance in dentin resorption assays, potentially reflecting inefficient bone resorption in vivo. It will be important to determine how this defect contributes to the development of cysts and spontaneous fractures in bones of Nasu-Hakola disease patients (9). Consistent with our results, defective development and resorptive function of OCs have been recently observed in DAP12-deficient mice (23). Thus, TREM-2/DAP12 is an essential element in a unique ...
Aseptic loosening (AL) because of osteolysis may be the primary reason behind joint prosthesis failure. the next factors were noticed: Interleukins 6 and 1 (IL16 and ), Tumor Necrosis Element (TNF), nuclear element kappa-light-chain-enhancer of triggered B cells (NFB), Nuclear element of triggered T-cells, cytoplasmic 1 (NFATC1), Cathepsin K (CATK) and Tartrate-resistant acidity phosphatase (Capture). Titanium (Ti) and Polyethylene (PE) had been the most researched contaminants, displaying that Ti up-regulated osteoclastogenesis and swelling related genes, while PE up-regulated osteoclastogenesis related genes mainly. in ZrO2 than Ti[54]0.05, 0.5, 1 mg/mL Ti alloy contaminants (? 0.52 m)SFs from OA pzProtein amounts (IRE1-, CHOP, RANKL, OPG, sRANKL) Gene expression ((at the best concentration)[45]0.1 mg/mL Ti particles (? 3.6 m)Mice BMMOCs number Bone resorption assay Gene expression ( cell viability, ALP, COLL I, OCN, mineralization, CMKBR7 membrane damage viability OBs, BMMs: (at 7 days), (at ...
Bone resorption relies on the extracellular acidification function of V-ATPase (vacuolar-type proton-translocating ATPase) proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of the osteoclast-specific ruffled border V-ATPases remains largely unknown. In the present study, we found that the V-ATPase subunit Atp6v1c1 (C1) is highly expressed in osteoclasts, whereas subunits Atp6v1c2a (C2a) and Atp6v1c2b (C2b) are not. The expression level of C1 is highly induced by RANKL [receptor activator for NF-κB (nuclear factor κB) ligand] during osteoclast differentiation; C1 interacts with Atp6v0a3 (a3) and is mainly localized on the ruffled border of activated osteoclasts. The results of the present study show for the first time that C1-silencing by lentivirus-mediated RNA interference severely impaired osteoclast acidification activity and bone resorption, whereas cell differentiation did not appear to be affected, which is similar to a3 silencing. The F-actin ...
In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression). Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment
Osteoclasts demonstrate ontogenetic changes in site specificity. Figure 3 and Table 1 clearly show that TRAP-positive osteoclasts are absent during initial postnatal development. This does not preclude the presence of osteoclasts at this time. In fact, Rice et al. (1997) have shown MMP-9-positive osteoclasts at these ages. The probable reason for this is because the calvarial bone being deposited at these newborn stages is low in mineral content. The matrix metalloproteinase, MMP-9, is thought to be sufficient for the early requirements of bone resorption. Later in postnatal development as bone becomes more densely mineralized, TRAP-positive osteoclasts would be required for resorption. Congruent with this explanation, osteoclasts are observed along concave and straight sagittal suture margins at 10 days postnatal. By 21 days postnatal, one can observe osteoclasts along convex margins as well. The occurrence of osteoclasts along convex and concave regions increases incrementally until 42 days ...
Aseptic loosening (AL) because of osteolysis may be the primary reason behind joint prosthesis failure. the next factors were noticed: Interleukins 6 and 1 (IL16 and ), Tumor Necrosis Element (TNF), nuclear element kappa-light-chain-enhancer of triggered B cells (NFB), Nuclear element of triggered T-cells, cytoplasmic 1 (NFATC1), Cathepsin K (CATK) and Tartrate-resistant acidity phosphatase (Capture). Titanium (Ti) and Polyethylene (PE) had been the most researched contaminants, displaying that Ti up-regulated osteoclastogenesis and swelling related genes, while PE up-regulated osteoclastogenesis related genes mainly. in ZrO2 than Ti[54]0.05, 0.5, 1 mg/mL Ti alloy contaminants (? 0.52 m)SFs from OA pzProtein amounts (IRE1-, CHOP, RANKL, OPG, sRANKL) Gene expression ((at the best concentration)[45]0.1 mg/mL Ti particles (? 3.6 m)Mice BMMOCs number Bone resorption assay Gene expression ( cell viability, ALP, COLL I, OCN, mineralization, CMKBR7 membrane damage viability OBs, BMMs: (at 7 days), (at ...
The resorption of a medical implant can be controlled with the use of particles embedded in a resorbable bulk material forming the implant or portion thereof. The implant can be removed from a body of a mammal by natural biological mechanisms after use. The resorption of the implant can involve swelling and/or hydrolyzing of the particles within the implant upon contact with a body fluid such that porosity and flow of fluid within the bulk material of the implant is increased. Resorption of the implant may also involve the use of particles with magnetic properties embedded within the implant such that an applied magnetic field causes the particles to vibrate within the bulk material thereby increasing the porosity and thus the flow of fluid, hence facilitating resorption of the implant. The resorption rate of the implant can be controlled by modulating swelling, hydrolysis, or movement of the embedded particles.
An osteoclast (from the Greek words for "bone" (ὀστέον), and "broken" (κλαστός)) is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodelling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium. An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth. An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have five nuclei and are about 150-200 µm in diameter. When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. These may have dozens of nuclei, and typically express major osteoclast proteins but have significant ...
In GAP, generalized bone destruction is present that ranges from mild crestal bone resorption to severe alveolar bone ... Bone resorption agents Inhibitors of bone formation Antibiotic resistance Fc-binding proteins Stimulators of inflammatory ... "Five-year alveolar bone level changes in women of varying skeletal bone mineral density and bone trabeculation". Oral Surgery, ... and usually horizontal bone pattern of bone loss at the interproximal surface of the incisors as the bone is thinner than at ...
Reduce bone resorption, increase bone formation. *Protein synthesis *Increase hepatic production of binding proteins ... In addition, estrogens are responsible for bone maturation and maintenance of bone mineral density throughout life. Due to ... Bone/skeletal system[edit]. Estrogens are responsible for both the pubertal growth spurt, which causes an acceleration in ... Some estrogens are also produced in smaller amounts by other tissues such as the liver, pancreas, bone, adrenal glands, skin, ...
... increased bone resorption, allowing flow of calcium from bone to blood reduced kidney clearance of calcium increased intestinal ... clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal ... This increases bone resorption. In chronic kidney failure the problem is more specifically failure to convert vitamin D to its ... A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption. Parathyroid adenomas are very rarely ...
Bone resorption Gallium Nitrate monograph. Lexi-Comp Online, Lexi-Drugs Online, Lexi-Comp Inc. Hudson, OH. Available at: [1]. ... Also, the increased concentration of gallium in the bone leads to increasing the synthesis of collagen as well as the formation ... It works by preventing the breakdown of bone through the inhibition of osteoclast activity, thus lowering the amount of free ... J Natl Cancer Inst 83: 1582-1584, 1991 Warrell RP Jr: Gallium nitrate for the treatment of bone metastases. Cancer 80: 1680- ...
... has shown to have positive effects on bone turnover. It has aided in decreasing bone resorption and increasing bone ... This was indicated by a decrease in the levels of two bone resorption markers (deoxypyridinoline and N-telopeptide) and an ... in pro-inflammatory responses and an increase in anti-inflammatory responses which indicates a reduction in bone resorption as ... Ribonuclease-enriched lactoferrin has been used to examine how lactoferrin affects bone. ...
Two different kinds of bone resorption are possible: direct resorption, which starts from the lining cells of the alveolar bone ... "Bone disposition, bone resorption, and osteosarcoma". Orthopedic Research Society. 28: 1142-8. doi:10.1002/jor.21120. PMID ... This is called bone remodeling. Bone remodeling is a biomechanical process responsible for making bones stronger in response to ... Bone deposition occurs in the distracted periodontal ligament. Without bone deposition, the tooth will loosen and voids will ...
reduce bone resorption. *increase hepatic production of binding proteins. Coagulation: *increase circulating level of factors 2 ... Assist in thyroid function and bone growth by osteoblasts. *Resilience in bone, teeth, gums, joint, tendon, ligament and skin ... Construct bone, reduce blood Ca2+ Cholecystokinin. CCK. duodenum. CCK receptor. Release of digestive enzymes from pancreas ... libido, Anabolic: growth of muscle mass and strength, increased bone density, growth and strength, Virilizing: maturation of ...
This may cause bone pain and tenderness, due to increased bone resorption. Due to increased circulating calcium, there may be ... Hyperparathyroidism and hypoparathyroidism, characterized by alterations in the blood calcium levels and bone metabolism, are ... as well as bone physiology. Parathyroid hormone has effects antagonistic to those of calcitonin. Calcium. PTH increases blood ... to break down bone and release calcium. PTH increases gastrointestinal calcium absorption by activating vitamin D, and promotes ...
Salo, J.; Lehenkari, P.; Mulari, M.; Metsikkö, K.; Väänänen, H. K. (1997). "Removal of osteoclast bone resorption products by ...
Compounds of zinc Zinc deficiency Zinc toxicity Yamaguchi M (1995). "beta-Alanyl-L-histidinato zinc and bone resorption". ... It has a stimulatory effect on bone formation and a restorative effect on bone loss under various pathophysiologic conditions. ... Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate ... The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. ...
Kobayashi, Yasuhiro; Maeda, Kazuhiro; Takahashi, Naoyuki (July 2008). "Roles of Wnt signaling in bone formation and resorption ... Under certain circumstances adenosine stimulates bone destruction and in other situations it promotes bone formation, depending ... Adenosine is very relevant in bone metabolism, as it plays a role in formation and activation of both osteoclasts and ... In TGF-β (Transforming Growth Factor β) pathway, BMP (Bone Morphogenic Protein), Activin and Nodal ligands bind to their ...
1984). Resorption of bone by isolated rabbit osteoclasts. J Cell Science 66: 383 - 399 PMID 6746762 Athanasou NA, Quinn J. ( ... With TJ Chambers he developed the osteoclast lacunar bone resorption assay system. His work was the first to show that the ... This led to the discovery of cellular and molecular mechanisms of pathological bone resorption associated with primary and ... 1996) Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis. Ann Rheum ...
PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, ... "A potent inhibitor of osteoclastic bone resorption within a highly conserved pentapeptide region of parathyroid hormone-related ... "A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts". ... Miao et al. showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, ...
Parathyroid hormone (in high concentrations in the blood) causes bone resorption, releasing calcium into the plasma. This is a ... namely high plasma ionized Ca2+ levels and the resorption of bone, which can lead to spontaneous fractures. The abnormally high ... The effector organs of the first homeostatic mechanism are the bones, the kidney, and, via a hormone released into the blood by ... This hormone acts primarily on bone, causing the rapid removal of calcium from the blood and depositing it, in insoluble form, ...
These include: increased rate of bone turnover with resorption exceeding formation; an initial rapid phase of bone loss ... greater loss of cancellous bone than cortical bone; reduced intestinal calcium absorption; some protection against bone loss by ... Kalu DN (December 1991). "The ovariectomized rat model of postmenopausal bone loss". Bone Miner. 15 (3): 175-91. doi:10.1016/ ... Van Linden JC; Waarsing JH; Weinans H. (2006). "The use of micro-CT to study bone architecture dynamics noninvasively". Drug ...
Methods for the treatment of bone resorption disorders, including osteoporosis". "USPTO: Acid sphingomyelinase gene". "USPTO: ...
Research areas include: regulation of bone remodeling; mechanisms of bone formation, bone resorption and mineralization; and ... The programs emphasize the application of fundamental knowledge of bone cell biology to the development of drug and gene ... Research is managed under three main areas: Bone Biology and Diseases-supports research to better understand genetic and ... The aim of these studies is to understand cells and signals influencing tooth, bone, and periodontal ligament development. ...
Osteoclasts become highly active during MM, leading to bone resorption and secretion of various MM survival factors. They ... July 1994). "Bone marrow angiogenesis and progression in multiple myeloma". Br. J. Haematol. 87 (3): 503-8. doi:10.1111/j.1365- ... The secretion of IL-6 by bone marrow stromal cells (BMSC) and the secretion of the adhesion molecules VCAM-1, ICAM-1 and LFA, ... They discovered increased bone marrow angiogenesis correlates with myeloma growth and supporting stromal cells are a ...
Tanaka S, Nakamura K, Takahasi N, Suda T (Dec 2005). "Role of RANKL in physiological and pathological bone resorption and ...
Tanaka S, Nakamura K, Takahasi N, Suda T (2006). "Role of RANKL in physiological and pathological bone resorption and ...
"Serum leptin as a determinant of bone resorption in healthy postmenopausal women". Bone. 33 (5): 847-852. doi:10.1016/j.bone. ...
X-rays may reveal bone resorption and degenerative changes in the joint. These findings in the presence of intact skin and loss ... The resulting hyperemia leads to increased osteoclastic resorption of bone, and this, in concert with mechanical stress, leads ... bone resorption, and eventual deformity due to loss of sensation. Onset is usually insidious. If this pathological process ... commonly seen at the distal aspect of the metatarsals Diabetic osteolysis Bone resorption Once the process is recognized, it ...
The test used to detect the CTX marker is called the Serum CrossLaps, and it is more specific to bone resorption than any other ... Lower values represent varying degrees of suppression of normal bone turnover, sometimes also called bone remodeling or bone ... A new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of ... Although a number of surrogate biomarkers exist for measuring the metabolic products of bone resorption, the serum CTX marker ...
Dental abscesses can cause resorption of bone and consequent loss of attachment. Depending on the type of abscess, this loss of ... This is because the tooth is not fused to the bones of the jaws, but is connected to the sockets by the periodontal ligament. ... Generally, the degree of mobility is inversely related to the amount of bone and periodontal ligament support left. Grace & ... This is caused by gradual resorption of their roots, stimulated by the developing permanent tooth underneath. Abnormal, ...
Normal bone growth is achieved by a balance between bone formation by osteoblasts and bone resorption (breakdown of bone matrix ... As bone resorption fails while bone formation continues, excessive bone is formed. Mutations in at least nine genes cause the ... These cells break down bone tissue during bone remodeling, a normal process in which old bone is removed and new bone is ... old bone is not broken down as new bone is formed. As a result, bones throughout the skeleton become unusually dense. The bones ...
positive regulation of bone resorption. • regulation of osteoclast differentiation. • transforming growth factor beta receptor ...
... a structure that resembles bone. However, cementum is more resistant to resorption than bone. There are a number of theories as ... External resorption, or root resorption, is the breakdown or destruction and subsequent loss of the root structure of a tooth. ... Severe root resorption is very difficult to treat and often requires the extraction of teeth. Root resorption occurs as a ... Types include external resorption and internal resorption. It can be due to trauma, infection, or hyperplasia. Internal ...
During childhood, bone formation exceeds resorption. As the aging process occurs, resorption exceeds formation. Bone resorption ... Bone reabsorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and ... In some cases where bone resorption outpaces ossification, the bone is broken down much faster than it can be renewed. The bone ... Light weight bearing exercise tends to eliminate the negative effects of bone resorption. Bone resorption is highly stimulated ...
... the second volume in the series Topics in Bone Biology, deals with the osteoclast, the bone-resorbing cell, its origins, its ... Bone Resorption, the second volume in the series Topics in Bone Biology, deals with the osteoclast, the bone-resorbing cell, ... Bone resorption Cytokines Internist Osteoclasts bone complication nutrition pathophysiology physiology Editors and affiliations ... Because osteoporosis may be considered a disease in which the bone resorption rate exceeds formation, a separate chapter deals ...
... to active bone resorption surfaces in both physiological and pathological situations and may play a key role in bone resorption ... Monocyte-induced osteoclastic bone resorption may play an important role in physiologic bone remodeling and in bone destruction ... Bone matrix sustained comparable resorption as demonstrated by a 2-fold decrement in the extracted dry weights of the bones ... to active bone resorption surfaces in both physiological and pathological situations and may play a key role in bone resorption ...
7) report that increased production of TNF-α by T cells in bone marrow mediates the increased bone resorption and bone loss in ... The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 2000. ... These factors increase bone resorption, mainly by increasing the pool size of pre-OCs in bone marrow (2, 3), and are ... The mechanisms of estrogen regulation of bone resorption. B. Lawrence Riggs Endocrine Research Unit, Mayo Clinic and Foundation ...
This study establishes that bone formation and/or bone mass do not control the extent of bone resorption in vivo. ... Generally, it has been assumed that bone formation and bone resorption functions are linked mechanistically during bone ... Dissociation between bone resorption and bone formation in osteopenic transgenic mice. David A. Corral, Michael Amling, ... Dissociation between bone resorption and bone formation in osteopenic transgenic mice. David A. Corral, Michael Amling, ...
... the administration of a bone resorption inhibitor during a period of approximately 12 to 36 months. ... The invention relates to a combined pharmaceutical preparation comprising parathyroid hormone and a bone resorption inhibitor, ... This is a process where bone resorption is closely linked to bone formation, through the concerted action of the bone active ... Bone growth factors and inhibitors of bone resorption for promoting bone formation. ...
Did you realize that bone loss actually begins around the age of thirty-five? The first obvious clue is when we begin to lose ... In addition to this, I would recommend a Bone Resorption Test. This is a must test. The bone resorption test can be done ... Unfortunately by the time a bone density change is noted it may already be too late. The bone resorption test is a urine test ... Bone resorption test for osteoporosis. By Dr. Teresa C. Hill. For the Journal-Advocate ...
High sodium chloride intake exacerbates immobilization-induced bone resorption and protein losses.. Frings-Meuthen P1, ... exacerbates disuse-induced bone and muscle loss by causing further protein wasting and an increase in bone resorption. Changes ... greater excretion of the bone resorption markers COOH- (CTX) and NH(2)- (NTX) terminal telopeptide of type I collagen in HDBR ... Serum concentrations of the bone formation markers bone-specific alkaline phosphatase (bAP) and NH(2)-terminal propeptide of ...
Bone Miner. 1991 Mar;12(3):167-79. Research Support, U.S. Govt, P.H.S. ... Bone Miner. 1991 Mar;12(3):167-79.. Bone particles from gallium-treated rats are resistant to resorption in vivo.. Donnelly R1 ... Resorption of bone particles containing 0.39 micrograms Ga/mg bone was significantly inhibited relative to control particles. ... Day 21 was chosen as a single time point for the comparison of the extent of resorption of gallium-containing and control bone ...
... or bone mass) at least 2.5 standard deviations below peak bone mass (defined as the bone mass achieved by healthy adults aged ... Bisphosphonate bone-resorption inhibitors. Class Summary. These agents decrease bone resorption and prevent bone loss from ... Pamidronate inhibits both normal and abnormal bone resorption. It appears to inhibit bone resorption without as much impact on ... Prediction of bone loss with biochemical bone markers. Adapted from Ross PD, Knowlton W. Rapid bone loss is associated with ...
Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture ... Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture ... Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture ... Thyrocalcitonin Inhibition of Bone Resorption Induced by Parathyroid Hormone in Tissue Culture ...
Biochemical monitoring of bone metabolism depends upon measurement of enzymes and proteins released during bone formation and ... The field of bone turnover markers has developed considerably in the past decade. ... Bone Resorption Markers. The most useful markers of bone resorption are degradation products derived from the enzymatic ... Markers of bone resorption predict hip fracture in elderly women, the EPIDOS Prospective Study. J Bone Miner Res 1996 Oct; 11( ...
... osteoclasts are breaking down bone and releasing minerals, to transfer calcium from the bone fluid into the blood. - Stock ... Keywords: anatomical, anatomy, artwork, bone, bone minerals, decalcified, drawing, human bone, illustration, medical, medical ... Caption: Illustration showing bone resorption; osteoclasts are breaking down bone and releasing minerals, to transfer calcium ... illustration, musculoskeletal, musculoskeletal system, osteoclast, osteoclasts, remodeling, resorb, resorption, skeletal, ...
Increased bone resorption in patients with CAH has been noted in the past and has been related to alterations in receptor ... Bone resorption control of tooth eruption and root morphogenesis: Involvement of the receptor activator of NF-κB (RANK). J Cell ... Recently, bone resorption has been found to be correlated with accelerated eruption of teeth in mice.17 ... This report suggests that early exfoliation of primary teeth can be a side effect of bone resorption in patients with CAH. ...
1, 3, 4). These cytokines increase bone resorption mainly by increasing the pool size of preosteoclasts in bone marrow (1, 3, 4 ... The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J. Bone Miner. Res. ... The bone lining cell: its role in cleaning Howships lacunae and initiating bone formation. J. Bone Miner. Res. 2002. 17:77-90 ... The bone remodeling compartment: a circulatory function for bone lining cells. J. Bone Miner. Res. 2001. 16:1583-1585. View ...
Orthopedics , OCOSH Classification , Bone Diseases , Bone Resorption. Bone Resorption (Subscribe) Bone loss due to normal or ... OCOSH Classification: Bone Diseases: Bone Resorption - OCOSH Classification: Bone Diseases: Metabolic Bone Diseases ... OCOSH Classification: Bone Diseases: Bone Resorption - OCOSH Classification: Investigations: Radiology - General: Radiology - ... SNOMED-CT Bone resorption disorder (finding) Concept ID: 68921007. OCOSH Code: D000387 68921007 M89.5 BD_BR_ANH. Osteolysis (28 ...
Bone Resorption Summary Description: Bone loss due to osteoclastic activity.. Also Known As: Bone Losses, Osteoclastic; Bone ... Resorptions; Loss, Osteoclastic Bone; Losses, Osteoclastic Bone; Osteoclastic Bone Losses Show All ,, Networked: 12154 relevant ... Key Therapies for Bone Resorption. Efficacy Chart ,, * Ovariectomy (Oophorectomy) : 6 outcomes 21 studies in 146 results ... Key Drugs and Agents for Bone Resorption. Efficacy Chart ,, Drugs and Important Biological Agents (IBA) related to treatments: ...
c-Cbl is downstream of c-Src in a signalling pathway necessary for bone resorption.. Tanaka S1, Amling M, Neff L, Peyman A, ... In vitro bone resorption by osteoclast-like cells (OCLs) is inhibited by both c-src and c-cbl antisense oligonucleotides. ... These results indicate that c-Cbl may act downstream of c-Src in a signalling pathway that is required for bone resorption. ... The primary defect in mice lacking the c-src gene is osteopetrosis, a deficiency in bone resorption by osteoclasts. Osteoclasts ...
... Bachir Benarba ... The aim of the present study was to investigate the response of bone resorption markers to A. longa intake by Algerian breast ... 1 g of A. longa intake resulted in significant rise of renal serum markers and a pronounced increase of bone resorption markers ... The intake of A. longa roots is detrimental for kidney function and resulted in high bone resorption, maybe due to the ...
TRAF3 protein levels decrease in bone and bone marrow during aging in mice and humans. Development of drugs to prevent TRAF3 ... microscopic sites of effete or damaged bone are degraded on bone surfaces by osteoclasts and subsequently replaced by new bone ... microscopic sites of effete or damaged bone are degraded on bone surfaces by osteoclasts and subsequently replaced by new bone ... Chloroquine also inhibits bone destruction induced by ovariectomy and parathyroid hormone in mice in vivo. Mice genetically ...
... time course of indices of bone resorption was investigated using 13-day-old embryonic chick calvaria. When calvariae were ... To clarify what kind of process participates in bone resorption, ... The effect of cadmium of bone resorption in tissue culture. ... To clarify what kind of process participates in bone resorption, time course of indices of bone resorption was investigated ... On the possibility that bone matrix collagen is removed prior to bone mineral during active cell-mediated bone resorption. In: ...
Check drug and medication side effect reports associated with Resorption Bone Increased ... What drug can cause Resorption Bone Increased as their side effect? ... bone pain, fracture , resorption bone increased More. atacand. Episodes: 1. hypertension.cough, muscle spasms, resorption bone ... periodontitis, resorption bone increased More. cymbalta. Episodes: 1. depression .bone disorder, resorption bone increased, ...
Results Most bone resorption occurred at pre-existing cavities within the bone in the periphery around the pressurized region, ... Fluid pressure and flow as a cause of bone resorption. Fahlgren, Anna Linköping University, Department of Clinical and ... The localization of the resorptive lesions suggests that high-velocity fluid flow is important for bone resorption induced by ... Background Unstable implants in bone become surrounded by an osteolytic zone. This is seen around loose screws, for example, ...
Purpose: The aim of this study was to compare vertical and horizontal mandibular alveolar bone resorption by measuring bone ... Conclusions: Vertical and horizontal alveolar bone resorption was found to be higher in the RPD wearing patients when comparing ... The Effect of Removable Partial Dentures on Alveolar Bone Resorption: A Retrospective Study with Cone-Beam Computed Tomography ... mean vertical and horizontal mandibular bone resorption was significantly higher in RPD wearers than in non-wearers (p , 0.05). ...
  • Tooth resorption is a process by which all or part of a tooth structure is lost due to activation of the body's innate capacity to remove mineralized tissue, as mediated via cells such as osteoclasts. (wikipedia.org)
  • The most common hypothesis is that because cementum is harder and more mineralized than bone, and has anti-angiogenic properties, blood vessels are inhibited from forming adjacent to cementum, which in turn prevents access to osteoclasts. (wikipedia.org)
  • In vitro bone resorption by osteoclast-like cells (OCLs) is inhibited by both c-src and c-cbl antisense oligonucleotides. (nih.gov)
  • Delaissé JM, Eeckhout Y and Vaes G: In vivo and in vitro evidence for the involvement of cysteine proteinases in bone resorption. (springer.com)
  • In conclusion, the in vitro and in vivo experimental results indicate that [email protected](HA-PASP) CL has great potential in the treatment of breast cancer bone metastasis. (rsc.org)
  • These results indicate that SFN is a novel inhibitor of breast cancer-induced osteolytic bone resorption in vitro and in vivo . (aacrjournals.org)
  • Our study indicates the importance of using different in vitro approaches for studies of regulation of osteoclastogenesis by S. aureus to obtain better understanding of the complex mechanisms of S. aureus bone destruction in vivo . (diva-portal.org)
  • Since the susceptibility to, or the severity of inflammation-associated bone diseases are likely related to differences in the tissue response, and the mechanisms by which PAMPs interact with bone cells are not fully understood, we aimed to elucidate the importance of different TLRs for inflammation induced bone loss by conducting in vitro and in vivo investigations. (diva-portal.org)
  • To explore other possible functions of these molecules, we have examined whether TIMPs in FCS affect osteoclastic bone resorption in vitro. (nii.ac.jp)
  • Clopidogrel (Plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo. (semanticscholar.org)
  • Extracellular nucleotides block bone mineralization in vitro: evidence for dual inhibitory mechanisms involving both P2Y2 receptors and pyrophosphate. (semanticscholar.org)
  • In order to study bone remodelling in vitro, we cultivated two precursor cellline types in a model coculture system on synthetic hydroxyapatite ceramic (HA) for 14 days. (semanticscholar.org)
  • In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. (elsevier.com)
  • In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors. (elsevier.com)
  • Low-dose doxycycline inhibits bone resorptionassociated with apical periodontitis Z. Metzger1,2, D. Belkin1, N. Kariv3, M. Dotan1 & A. Kfir21Department of Oral Biology and 2Department of Endodontology, The Maurice and Gabriela Goldschleger School of DentalMedicine, 3Glasberg Tower for Medical Research, Tel Aviv University, Tel Aviv, Israel was determined and used to compare the groups. (healthdrugpdf.com)
  • Cytokines with bone-resorbing activity include IL 1 beta (pI 7), IL 1 alpha (pI 5), tumor necrosis factor (TNF), and lymphotoxin (LT). Possible interaction between IL 1 beta, the major mediator with osteoclast-activating factor (OAF) activity, and other cytokines was studied. (jimmunol.org)
  • Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. (unboundmedicine.com)
  • Inflammatory bone loss is accompanied by osteoclast formation induced by bone-resorbing cytokines, but the mechanism of PGE2 production and bone resorption in vivo is not fully understood. (rupress.org)
  • S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. (diva-portal.org)
  • S. aureus also increased the expression of proinflammatory cytokines and prostaglandins in parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. (diva-portal.org)
  • Simultaneous addition of the two cytokines showed similar bone-resorbing activity at much lower doses. (nii.ac.jp)
  • they participate in immune responses, and secrete cytokines that can affect their own functions and those of other cells in inflammatory and neoplastic processes affecting bone. (begellhouse.com)
  • To assess the expression of cytokines and genes invloved in osteoclastogenesis on the bone tissues, we set up the system of in situ hybridization using decalcified bone specimen. (nii.ac.jp)
  • RANKL is a member of the TNF family of cytokines and plays a key role in bone resorption. (biomedcentral.com)
  • Nevertheless, presence of bone resorption indicates disease whilst locally produced inflammatory cytokines, such as IL1b healing is monitored by its reversal and by reduction ofthe periapical radiolucency. (healthdrugpdf.com)
  • They conclude that while M-CSF and RANKL are essential for physiologic OC renewal, TNF-α plays a key causal role in the bone loss associated with E deficiency. (jci.org)
  • Increased bone resorption in patients with CAH has been noted in the past and has been related to alterations in receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG). (aappublications.org)
  • Morphometrical analysis of alveolar bone loss demonstrated that CBD-treated animals presented a decreased alveolar bone loss and a lower expression of the activator of nuclear factor-kappaB ligand RANKL/RANK. (unboundmedicine.com)
  • Background Bone loss in inflammatory diseases like periodontitis, rheumatoid arthritis, septic arthritis and loosened joint prosthesis or tooth implants is being considered a consequence of cytokine induced RANKL and subsequent enhanced osteoclast formation. (bmj.com)
  • Conclusion These data show that stimulation of TLR2 results in bone resorption mediated by increased RANKL in osteoblasts and may be one mechanism for developing inflammatory bone loss. (bmj.com)
  • S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. (diva-portal.org)
  • Bone loss in inflammatory diseases is considered a consequence of cytokine induced RANKL and subsequent enhanced osteoclast formation. (diva-portal.org)
  • In particular, macrophage colony-stimulating factor, RANKL, TNF, IL-1 and IL-17 may play dominant roles in the pathogenesis of arthritis-associated bone loss. (biomedcentral.com)
  • Extensive research within the last decade has revealed that RANKL, a member of the tumor necrosis factor superfamily, plays a major role in cancer-associated bone resorption and thus is a therapeutic target. (isharonline.org)
  • RANKL, a member of the TNF family, is expressed on the mesenchymal cells and on activated T cells, which illustrates the tight link between immune activation and bone ( 7 ). (jimmunol.org)
  • High NaCl intake during immobilization exacerbates disuse-induced bone and muscle loss by causing further protein wasting and an increase in bone resorption. (nih.gov)
  • Estrogen deficiency is associated with an increase in bone resorption over bone formation, leading to excessive and sustained bone loss. (jci.org)
  • During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. (menopause.org.au)
  • The magnitude of the increase in bone resorption is inversely associated with BMI. (menopause.org.au)
  • During the perimenopausal phase, there is an increase in bone resorption due to the decline in ovarian function. (menopause.org.au)
  • Mice deficient in Slit3 or its receptor, Robo1, exhibited osteopenic phenotypes due to a decrease in bone formation and increase in bone resorption. (jci.org)
  • To determine whether bone resorption is influenced by bone formation in vivo , tg mice were generated with a 1.3-kb fragment of the mouse OG2 promoter, which was used to drive expression of Hsv-Tk (refs. (pnas.org)
  • Recently, bone resorption has been found to be correlated with accelerated eruption of teeth in mice. (aappublications.org)
  • Osteoclast number per bone perimeter from control and Ror2 ΔOcl/ΔOcl mice. (sciencemag.org)
  • It stimulates bone resorption in rat calvaria cultures via its lipopolysaccharide [ 6 ] and causes osteoclastic bone resorption in the hind paws of mice and alveolar bone resorption in rats [ 7 ]. (hindawi.com)
  • Objective To assess the role of bone remodelling in OA by studying the effect of bisphosphonate on OA development in mice with high bone remodelling. (bmj.com)
  • meanwhile, [email protected](HA-PASP) CL significantly decreased the tumor volume and bone resorption in tumor-bearing mice without causing obvious systemic toxicity. (rsc.org)
  • Using cytosolic phospholipase A2α (cPLA2α)-null mice, we examined the role of cPLA2α in PGE2 synthesis and bone resorption. (rupress.org)
  • In cPLA2α-null mice, however, LPS-induced bone loss could not be observed at all. (rupress.org)
  • RMA also inhibited the increase of bone resorption in ovariectomised mice. (nii.ac.jp)
  • This study has attempted to clarify the mechanisms of cartilage-to-bone replacement in endochondral bone formation of long bones and of tooth morphegesis in osteosclerotic (oc/oc) mice by means of light and electron microscopy. (nii.ac.jp)
  • In oc/oc mice, multinucleated osteoclastic cells lacked both ruffled borders and clear zones facing the uncalcified cartilage, but formed only clear zones facing the calcified cartilage and bone matrix. (nii.ac.jp)
  • Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. (osteoporosis-studies.com)
  • showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, suggesting that PTHrP has a physiological function. (wikipedia.org)
  • Space shuttle flight STS-108 in 2001 tested the effects of osteoprotegerin on mice in microgravity, finding that it did prevent increase in resorption and maintained mineralization. (wikipedia.org)
  • Bone Resorption , the second volume in the series Topics in Bone Biology, deals with the osteoclast, the bone-resorbing cell, its origins, its enzymes, the regulation of osteoclast activity, and structural aspects of bone resorption. (springer.com)
  • The reason provided is that prolactin induces the release of PTH related peptide which enhances bone resorption, but is still under investigation. (wikipedia.org)
  • TIMs are thus capable of both low-grade (surface) and high-grade (lacunar) pathological bone resorption, a specific interaction with stromal cells being necessary for the latter to occur. (ox.ac.uk)
  • This led to the discovery of cellular and molecular mechanisms of pathological bone resorption associated with primary and secondary bone tumours, particularly breast cancer metastasis, Ewing sarcoma and giant cell-rich lesions such as giant cell tumour of bone and pigmented villonodular synovitis. (wikipedia.org)
  • However, susceptibility to periodontal disease and bone resorption can be the cause for primary exfoliation of primary teeth and accelerated eruption of its successors. (aappublications.org)
  • In the quest for materials that will prove useful in the treatment and prevention of periodontal disease, we investigated the preventive effects of an ethanol extract of Terminalia chebula (EETC) on DPB-induced inflammation and bone resorption. (isharonline.org)
  • This is because the tooth is not fused to the bones of the jaws, but is connected to the sockets by the periodontal ligament. (wikipedia.org)
  • Generally, the degree of mobility is inversely related to the amount of bone and periodontal ligament support left. (wikipedia.org)
  • The condition is diagnosed with radiographs (X-rays), which show loss of the periodontal ligament space and blending of the root with the bone. (wikipedia.org)
  • Kv1.3 is also considered a therapeutic target for the treatment of obesity, for enhancing peripheral insulin sensitivity in patients with type-2 diabetes mellitus, and for preventing bone resorption in periodontal disease. (wikipedia.org)
  • Selective blockade of voltage-gated potassium channels reduces inflammatory bone resorption in experimental periodontal disease. (wikipedia.org)
  • Enamel Matrix Protein These agents not only help improve wound healing but also stimulate regeneration of the lost bone, periodontal ligament and cementum restoring the complete periodontal attachment apparatus.Currently emdogain is the only approved host modulatory agent of this type. (wikipedia.org)
  • Inherent in most of the theories outlined above, is the idea that a force is generated in the periodontal ligament beneath unerupted teeth, and that this force physically drives teeth out through the bone. (wikipedia.org)
  • Bone is an especially prone metastatic site for breast cancer, and to block the vicious cycle between bone resorption and tumor growth is an important strategy for the treatment of breast cancer bone metastasis. (rsc.org)
  • In this paper, pH- and redox-sensitive as well as breast cancer bone metastasis-targeting nanoparticles ([email protected](HA-PASP) CL ) were prepared, and also their anti-tumor activity and anti-bone resorption effect were investigated in detail. (rsc.org)
  • The standard of therapeutic care for breast cancer patients with bone metastasis includes bisphosphonates (e.g., zoledronic acid), which have poor oral bioavailability, and a humanized antibody (denosumab). (aacrjournals.org)
  • Baylor College of Medicine's mission in this program is to develop strategies for stimulating new bone formation while The University of Texas M.D. Anderson Cancer Center is focused on bone loss in patients with cancer and the development of strategies to prevent spread of cancer (bone metastasis) into bone. (wikipedia.org)
  • The intake of A. longa roots is detrimental for kidney function and resulted in high bone resorption, maybe due to the reduction in renal function caused by the aristolochic acids contained in the roots. (hindawi.com)
  • Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. (nih.gov)
  • H. H. Malluche and M. C. Faugere, "Effects of 1,25(OH)2D3 administration on bone in patients with renal failure," Kidney International , vol. 29, supplement 38, pp. (hindawi.com)
  • The spectrum of bone disease in end-stage renal failure-an evolving disorder," Kidney International , vol. 43, no. 2, pp. 436-442, 1993. (hindawi.com)
  • clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia and renal osteodystrophy. (wikipedia.org)
  • Deficiency in Vitamin D or renal disease contributes to bone disorder such as in Osteomalacia in adult and Rickets in children. (wikipedia.org)
  • Monocyte-induced bone resorption is partly reversed by inhibitors of osteoclast function. (springer.com)
  • Inhibiting TP reduced the incidence of myeloma-induced osteolytic bone lesions, suggesting a new target for translation to the clinic, especially because certain TP inhibitors are already approved for human use. (sciencemag.org)
  • In medical research, quantification of the amount of bone resorbed areas is vital in understanding the resorptive capacity of the osteoclast under certain pathologic conditions, and its response to various treatments and pharmacological inhibitors. (iospress.com)
  • Two groups of bone resorption inhibitors? (cram.com)
  • What are the general uses of bone resorption inhibitors? (cram.com)
  • In order to provide a basis for understanding the underlying mechanisms of bone remodeling as it is mediated by PTH, we propose here a mathematical model of the process. (cellml.org)
  • Although the reason for the development of the early autoimmune reaction is unknown, the mechanisms that connect immune activation to bone destruction are better defined and built the basis of a new field of research called osteoimmunology ( 1 ). (jimmunol.org)
  • Growth Centers is an area in the bone that controls the overall growth of the bone from its locations through different signaling mechanisms. (wikipedia.org)
  • The drug prevents bone loss via mechanisms that are distinct from those of estrogens. (wikipedia.org)