Calcinosis
Pathologic deposition of calcium salts in tissues.
Vascular Calcification
Deposition of calcium into the blood vessel structures. Excessive calcification of the vessels are associated with ATHEROSCLEROTIC PLAQUES formation particularly after MYOCARDIAL INFARCTION (see MONCKEBERG MEDIAL CALCIFIC SCLEROSIS) and chronic kidney diseases which in turn increase VASCULAR STIFFNESS.
Calcification, Physiologic
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
Chondrocytes
Polymorphic cells that form cartilage.
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.
Epiphyses
Tibia
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.
Collagen Type X
A non-fibrillar collagen found primarily in terminally differentiated hypertrophic CHONDROCYTES. It is a homotrimer of three identical alpha1(X) subunits.
Bone Plates
Osteochondrodysplasias
Abnormal development of cartilage and bone.
Metatarsal Bones
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.
Aortic Diseases
Pathological processes involving any part of the AORTA.
Chondrogenesis
The formation of cartilage. This process is directed by CHONDROCYTES which continually divide and lay down matrix during development. It is sometimes a precursor to OSTEOGENESIS.
Tomography, X-Ray Computed
alpha-2-HS-Glycoprotein
A fetuin subtype that is synthesized by HEPATOCYTES and secreted into the circulation. It plays a major role in preventing CALCIUM precipitation in the BLOOD.
Vascular Diseases
Alkaline Phosphatase
Thiram
Bone Matrix
Femur
The longest and largest bone of the skeleton, it is situated between the hip and the knee.
Heart Valve Diseases
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.
Hypertrophy
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.
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).
Cell Differentiation
Ribs
A set of twelve curved bones which connect to the vertebral column posteriorly, and terminate anteriorly as costal cartilage. Together, they form a protective cage around the internal thoracic organs.
Osteoblasts
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
Calcium Carbonate
Dental Pulp Calcification
Growth Differentiation Factor 10
A growth differentiation factor that is closely-related in structure to BONE MORPHOGENETIC PROTEIN 3. Growth differentiation factor 10 is found at high levels in BONE, however it plays an additional roles in regulating EMBRYONIC DEVELOPMENT.
Bone Diseases, Developmental
Coronary Artery Disease
Receptor, Fibroblast Growth Factor, Type 3
A fibroblast growth factor receptor that regulates CHONDROCYTE growth and CELL DIFFERENTIATION. Mutations in the gene for fibroblast growth factor receptor 3 have been associated with ACHONDROPLASIA; THANATOPHORIC DYSPLASIA and NEOPLASTIC CELL TRANSFORMATION.
Skeleton
Cartilage, Articular
A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact.
Dwarfism
Hedgehog Proteins
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.
Aortic Valve
The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle.
Rickets
Disorders caused by interruption of BONE MINERALIZATION manifesting as OSTEOMALACIA in adults and characteristic deformities in infancy and childhood due to disturbances in normal BONE FORMATION. The mineralization process may be interrupted by disruption of VITAMIN D; PHOSPHORUS; or CALCIUM homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances.
SOXD Transcription Factors
Achondroplasia
An autosomal dominant disorder that is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand. (Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#100800, April 20, 2001)
Receptor, Parathyroid Hormone, Type 1
A parathyroid hormone receptor subtype that recognizes both PARATHYROID HORMONE and PARATHYROID HORMONE-RELATED PROTEIN. It is a G-protein-coupled receptor that is expressed at high levels in BONE and in KIDNEY.
In Situ Hybridization
Bone Morphogenetic Protein 2
A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.
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.
Cells, Cultured
Exostoses, Multiple Hereditary
Hereditary disorder transmitted by an autosomal dominant gene and characterized by multiple exostoses (multiple osteochondromas) near the ends of long bones. The genetic abnormality results in a defect in the osteoclastic activity at the metaphyseal ends of the bone during the remodeling process in childhood or early adolescence. The metaphyses develop benign, bony outgrowths often capped by cartilage. A small number undergo neoplastic transformation.
Collagen Type II
Uremia
A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.
Osteochondritis
Inflammation of a bone and its overlaying CARTILAGE.
Phosphorus
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.
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).
Kidney Failure, Chronic
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
Immunohistochemistry
Neural Plate
The region in the dorsal ECTODERM of a chordate embryo that gives rise to the future CENTRAL NERVOUS SYSTEM. Tissue in the neural plate is called the neuroectoderm, often used as a synonym of neural plate.
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.
Periosteum
Basal Ganglia Diseases
Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.
Rats, Sprague-Dawley
SOX9 Transcription Factor
A SOXE transcription factor that plays a critical role in regulating CHONDROGENESIS; OSTEOGENESIS; and male sex determination. Loss of function of the SOX9 transcription factor due to genetic mutations is a cause of CAMPOMELIC DYSPLASIA.
Monckeberg Medial Calcific Sclerosis
Hyperphosphatemia
A condition of abnormally high level of PHOSPHATES in the blood, usually significantly above the normal range of 0.84-1.58 mmol per liter of serum.
Atherosclerosis
Renal Dialysis
Gene Expression Regulation, Developmental
Tomography, Spiral Computed
Computed tomography where there is continuous X-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures.
Growth Disorders
Cell Proliferation
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Matrilin Proteins
PROTEOGLYCANS-associated proteins that are major components of EXTRACELLULAR MATRIX of various tissues including CARTILAGE; and INTERVERTEBRAL DISC structures. They bind COLLAGEN fibers and contain protein domains that enable oligomer formation and interaction with other extracellular matrix proteins such as CARTILAGE OLIGOMERIC MATRIX PROTEIN.
Aggrecans
Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces.
Aortic Valve Stenosis
A pathological constriction that can occur above (supravalvular stenosis), below (subvalvular stenosis), or at the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.
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.
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.
24,25-Dihydroxyvitamin D 3
A physiologically active metabolite of VITAMIN D. The compound is involved in the regulation of calcium metabolism, alkaline phosphatase activity, and enhances the calcemic effect of CALCITRIOL.
Calcium-Binding Proteins
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
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.
Risk Factors
Anthozoa
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.
Insulin-Like Growth Factor I
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
Femur Head
Phosphate Transport Proteins
Aorta, Abdominal
The aorta from the DIAPHRAGM to the bifurcation into the right and left common iliac arteries.
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.
Phenotype
Chickens
Extracellular Matrix
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)
Fibroblast Growth Factors
A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.
Cell Division
Bioprosthesis
Prosthesis, usually heart valve, composed of biological material and whose durability depends upon the stability of the material after pretreatment, rather than regeneration by host cell ingrowth. Durability is achieved 1, mechanically by the interposition of a cloth, usually polytetrafluoroethylene, between the host and the graft, and 2, chemically by stabilization of the tissue by intermolecular linking, usually with glutaraldehyde, after removal of antigenic components, or the use of reconstituted and restructured biopolymers.
Skull Base
Pseudoxanthoma Elasticum
An inherited disorder of connective tissue with extensive degeneration and calcification of ELASTIC TISSUE primarily in the skin, eye, and vasculature. At least two forms exist, autosomal recessive and autosomal dominant. This disorder is caused by mutations of one of the ATP-BINDING CASSETTE TRANSPORTERS. Patients are predisposed to MYOCARDIAL INFARCTION and GASTROINTESTINAL HEMORRHAGE.
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.
Chick Embryo
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.
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.