Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.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.Bone Demineralization Technique: Removal of mineral constituents or salts from bone or bone tissue. Demineralization is used as a method of studying bone strength and bone chemistry.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.Bone Resorption: Bone loss due to osteoclastic activity.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.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.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.Osteogenesis: The process of bone formation. Histogenesis of bone including ossification.Bone Regeneration: Renewal or repair of lost bone tissue. It excludes BONY CALLUS formed after BONE FRACTURES but not yet replaced by hard bone.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.Osteoblasts: Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.Bone Transplantation: The grafting of bone from a donor site to a recipient site.Bone Neoplasms: Tumors or cancer located in bone tissue or specific BONES.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.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.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.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.Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).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.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.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.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.Bone Diseases: Diseases of BONES.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.Skull: The SKELETON of the HEAD including the FACIAL BONES and the bones enclosing the BRAIN.Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Matrix Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.Fractures, Bone: Breaks in bones.Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee.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).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.Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.Osseointegration: The growth action of bone tissue as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants).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.X-Ray Microtomography: X-RAY COMPUTERIZED TOMOGRAPHY with resolution in the micrometer range.Bone Diseases, MetabolicBone 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.Periosteum: Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.Nuclear Matrix: The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52)Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.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.Haversian System: A circular structural unit of bone tissue. It consists of a central hole, the Haversian canal through which blood vessels run, surrounded by concentric rings, called lamellae.Implants, Experimental: Artificial substitutes for body parts and materials inserted into organisms during experimental studies.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.Tomography, X-Ray: Tomography using x-ray transmission.Osteonectin: Non-collagenous, calcium-binding glycoprotein of developing bone. It links collagen to mineral in the bone matrix. In the synonym SPARC glycoprotein, the acronym stands for Secreted Protein, Acidic and Rich in Cysteine.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Matrix Metalloproteinase 1: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving FIBRILLAR COLLAGEN. It can degrade interstitial collagens, types I, II and III.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.Ossification, Heterotopic: The development of bony substance in normally soft structures.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.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.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.Decalcification Technique: Removal of minerals from bones during bone examination.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.Ricinus: A plant genus of the family EUPHORBIACEAE, order Euphorbiales, subclass Rosidae. The seed of Ricinus communis L. is the CASTOR BEAN which is the source of CASTOR OIL; RICIN; and other lectins.Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium.Matrix Metalloproteinase 3: An extracellular endopeptidase of vertebrate tissues similar to MATRIX METALLOPROTEINASE 1. It digests PROTEOGLYCAN; FIBRONECTIN; COLLAGEN types III, IV, V, and IX, and activates procollagenase. (Enzyme Nomenclature, 1992)Fracture Healing: The physiological restoration of bone tissue and function after a fracture. It includes BONY CALLUS formation and normal replacement of bone tissue.Mandible: The largest and strongest bone of the FACE constituting the lower jaw. It supports the lower teeth.Bone Morphogenetic Protein 3: A bone morphogenetic protein that is found at high concentrations in a purified osteoinductive protein fraction from BONE. Bone morphogenetic protein 3 is referred to as osteogenin, however it may play a role in variety of developmental processes.Durapatite: The mineral component of bones and teeth; it has been used therapeutically as a prosthetic aid and in the prevention and treatment of osteoporosis.Minerals: 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)Humerus: Bone in humans and primates extending from the SHOULDER JOINT to the ELBOW JOINT.Tissue Scaffolds: Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.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.Diaphyses: The shaft of long bones.Tissue Engineering: Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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).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.Biocompatible Materials: Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function.Core Binding Factor Alpha 1 Subunit: A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION.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.Osteogenesis Imperfecta: COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.Calcium Phosphates: Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.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.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.Mesenchymal Stromal Cells: Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Etidronic Acid: A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth.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.Matrix Metalloproteinase 13: A secreted matrix metalloproteinase that plays a physiological role in the degradation of extracellular matrix found in skeletal tissues. It is synthesized as an inactive precursor that is activated by the proteolytic cleavage of its N-terminal propeptide.Awards and PrizesBiomechanical Phenomena: The properties, processes, and behavior of biological systems under the action of mechanical forces.Mice, Inbred C57BLMatrix Metalloproteinase 14: A transmembrane domain-containing matrix metalloproteinase. It is synthesized as an inactive zymogen that is activated by the action of PROPROTEIN CONVERTASES such as FURIN. Matrix metalloproteinase 14 plays a direct role in the cleavage of proteins in the pericellular environment. In addition, it can function indirectly by enzymatically activating the proprotein form of MATRIX METALLOPROTEINASE 15.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Matrix Metalloproteinase 7: The smallest member of the MATRIX METALLOPROTEINASES. It plays a role in tumor progression.Alveolar Bone Loss: Resorption or wasting of the tooth-supporting bone (ALVEOLAR PROCESS) in the MAXILLA or MANDIBLE.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.Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.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.Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures; OSTEITIS; SPLENOMEGALY with infarct; ANEMIA; and extramedullary hemopoiesis (HEMATOPOIESIS, EXTRAMEDULLARY).Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance.Wound Healing: Restoration of integrity to traumatized tissue.Polyurethanes: A group of thermoplastic or thermosetting polymers containing polyisocyanate. They are used as ELASTOMERS, as coatings, as fibers and as foams.Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.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.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.Osteosarcoma: A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Calcinosis: Pathologic deposition of calcium salts in tissues.Lumbar Vertebrae: VERTEBRAE in the region of the lower BACK below the THORACIC VERTEBRAE and above the SACRAL VERTEBRAE.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.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.Spine: The spinal or vertebral column.Spinal Fusion: Operative immobilization or ankylosis of two or more vertebrae by fusion of the vertebral bodies with a short bone graft or often with diskectomy or laminectomy. (From Blauvelt & Nelson, A Manual of Orthopaedic Terminology, 5th ed, p236; Dorland, 28th ed)Bone Morphogenetic Protein 7: A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.Matrix Metalloproteinases, Membrane-Associated: Matrix metalloproteinases that are associated with the CELL MEMBRANE, either through transmembrane domains or GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS. Membrane-type matrix metalloproteinases may act within the pericellular environment to influence the process of CELL MIGRATION.