The area between the EPIPHYSIS and the DIAPHYSIS within which bone growth occurs.
Polymorphic cells that form cartilage.
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.
The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united.
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.
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.
Implantable fracture fixation devices attached to bone fragments with screws to bridge the fracture gap and shield the fracture site from stress as bone heals. (UMDNS, 1999)
Abnormal development of cartilage and bone.
The five long bones of the METATARSUS, articulating with the TARSAL BONES proximally and the PHALANGES OF TOES distally.
A non-fibrillar collagen found primarily in terminally differentiated hypertrophic CHONDROCYTES. It is a homotrimer of three identical alpha1(X) subunits.
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.
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
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.
The process of bone formation. Histogenesis of bone including ossification.
A dithiocarbamate chemical, used commercially in the rubber processing industry and as a fungicide. In vivo studies indicate that it inactivates the enzyme GLUTATHIONE REDUCTASE. It has mutagenic activity and may induce chromosomal aberrations.
The region of the HAND between the WRIST and the FINGERS.
The longest and largest bone of the skeleton, it is situated between the hip and the knee.
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.
General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).
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.
Developmental bone diseases are a category of skeletal disorders that arise from disturbances in the normal growth and development of bones, including abnormalities in size, shape, structure, or composition, which can lead to various musculoskeletal impairments and deformities.
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.
The rigid framework of connected bones that gives form to the body, protects and supports its soft organs and tissues, and provides attachments for MUSCLES.
A genetic or pathological condition that is characterized by short stature and undersize. Abnormal skeletal growth usually results in an adult who is significantly below the average height.
A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.
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.
A subclass of closely-related SOX transcription factors. In addition to a conserved HMG-BOX DOMAIN, members of this group contain a leucine zipper motif which mediates protein DIMERIZATION.
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)
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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.
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.
Inflammation of a bone and its overlaying CARTILAGE.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.
Bone in humans and primates extending from the SHOULDER JOINT to the ELBOW JOINT.
A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.
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.
Increase in the mass of bone per unit volume.
Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.
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.
Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
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.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
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).
The development of bony substance in normally soft structures.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
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.
The hemispheric articular surface at the upper extremity of the thigh bone. (Stedman, 26th ed)
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).
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.
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.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
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.
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.
The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.
The performance of dissections with the aid of a microscope.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.

Spatiotemporal expression of alternatively spliced IGF-I mRNA in the rat costochondral growth plate. (1/822)

IGF-I acts as a local proliferation and maturation factor for chondrocytes in the growth plate. However, the expression of different alternative IGF-I mRNA classes in the growth plate has not been characterized. Using quantitative reverse transcription PCR, the abundance of each alternative IGF-I mRNA class in resting, proliferative and hypertrophic chondrocytes was measured in rat costochondral growth plates. Class 1Ea mRNA was the most abundant IGF-I transcript overall and was highly expressed in proliferative chondrocytes at 2 and 4 weeks of age; by 6 weeks, the majority of 1Ea mRNA expression had shifted to hypertrophic chondrocytes. Class 1Eb mRNA was the second most abundant transcript and its distribution was uniform across all the cell types at 2 weeks of age. The expression pattern changed with increasing age such that at 6 weeks a gradient existed with hypertrophic chondrocytes expressing higher levels of 1Eb than resting chondrocytes. Class 2Ea mRNA was constitutively expressed at low levels across the growth plate at all ages, while class 2Eb mRNA expression was negligible. The distribution of total IGF-I mRNA also shifted across growth plate cell types as the animals aged from 2 to 6 weeks. These findings suggest that IGF-I class 1 mRNA plays the predominant role in the maturation of the growth plate.  (+info)

The bcl-2 knockout mouse exhibits marked changes in osteoblast phenotype and collagen deposition in bone as well as a mild growth plate phenotype. (2/822)

Histological examination of long bones from 1-day-old bcl-2 knockout and age-matched control mice revealed no obvious differences in length of bone, growth plate architecture or stage of endochondral ossification. In 35-day-old bcl-2 knockout mice that are growth retarded or 'dwarfed'. the proliferative zone of the growth plate appeared slightly thinner and the secondary centres of ossification less well developed than their age-matched wild-type controls. The most marked histological effects of bcl-2 ablation were on osteoblasts and bone. 35-day-old knockout mouse bones exhibited far greater numbers of osteoblasts than controls and the osteoblasts had a cuboidal phenotype in comparison with the normal flattened cell appearance. In addition, the collagen deposited by the osteoblasts in the bcl-2 knockout mouse bone was disorganized in comparison with control tissue and had a pseudo-woven appearance. The results suggest an important role for Bcl-2 in controlling osteoblast phenotype and bone deposition in vivo.  (+info)

A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3. (3/822)

Achondroplasia, the most common form of dwarfism in man, is a dominant genetic disorder caused by a point mutation (G380R) in the transmembrane region of fibroblast growth factor receptor 3 (FGFR3). We used gene targeting to introduce the human achondroplasia mutation into the murine FGFR3 gene. Heterozygotes for this point mutation that carried the neo cassette were normal whereas neo+ homozygotes had a phenotype similar to FGFR3-deficient mice, exhibiting bone overgrowth. This was because of interference with mRNA processing in the presence of the neo cassette. Removal of the neo selection marker by Cre/loxP recombination yielded a dominant dwarf phenotype. These mice are distinguished by their small size, shortened craniofacial area, hypoplasia of the midface with protruding incisors, distorted brain case with anteriorly shifted foramen magnum, kyphosis, and narrowed and distorted growth plates in the long bones, vertebrae, and ribs. These experiments demonstrate that achondroplasia results from a gain-of-FGFR3-function leading to inhibition of chondrocyte proliferation. These achondroplastic dwarf mice represent a reliable and useful model for developing drugs for potential treatment of the human disease.  (+info)

Aberrant death in dark chondrocytes of the avian growth plate. (4/822)

Growth plate chondrocytes of embryonic chick femurs were examined by electron microscopy, cytophotometry and autoradiography. Apart from the well-described 'light' chondrocyte, a different 'dark' type of chondrocyte was present, comprising 10 - 35% of the cell population. They were found at all stages of chondrocyte differentiation and in all ages of the femurs studied. Well developed rough endoplasmatic reticulum and Golgi complex, many secretory vesicles, energetically active mitochondria and a lot of glycogen, indicating high activity of the cytoplasm, were combined with low RNA synthesis, gentle margination and scattered compaction of the chromatin. DNA cytometry revealed that most of dark cells were diploid, but 15 - 30% were tetraploid, with the absence of an S-phase. Substantial loss of DNA was found in about 10% of dark chondrocytes. The TUNEL reaction demonstrated a limited number of DNA strand breaks. Advanced dark cells possessed the nuclear features of both apoptosis and necrosis. Besides chromomeric-chromonemic compaction, a chromatin arrangement similar to that of prometaphase and metaphase, as well as amitotic nuclear segregation, all of them degenerative, were found. Our interpretation is that the dark chondrocytes undergo an aberrant type of cell death which may be combined with aberrant cell cycle. Cell death of dark chondrocytes is preceded by a pre-mortal burst of secretion.  (+info)

Growth plate cartilage formation and resorption are differentially depressed in growth retarded uremic rats. (5/822)

To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF). NX rats were growth retarded and severely uremic. Growth plate height (mean +/- SD) was much greater (P<0.05) in NX (868.4+/-85.4 microm) than SAL (570.1+/-93.5 microm) and SPF (551.9+/-99.7 microm) rats as a result of a higher (P<0.05) hypertrophic zone (661.0+/-89.7 versus 362.8+/-71.6 and 353.0+/-93.9 microm, respectively). The increased size of the growth plate was associated with a greater number of chondrocytes and modifications in their structure, particularly in the hypertrophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly (P<0.05) smaller (12080.4+/-1158.3 microm3) and shorter (34.1+/-2.5 microm) than those of SAL (16302.8+/-1483.4 microm3 and 37.8+/-2.0 microm) and SPF (14465.8+/-1521.0 microm3 and 36.3+/-1.8 microm). The interface between the growth plate cartilage and the metaphyseal bone appeared markedly irregular in NX rats. Kinetics of chondrocytes was also modified (P<0.05) in the NX rats, which had lower cell turnover per column per day (5.4+/-0.9), longer duration of hypertrophic phase (89.0+/-15.2 h), and reduced cellular advance velocity (7.4+/-2.2 microm/h) compared with SAL (8.0+/-1.6, 32.1+/-6.7 h, and 11.3+/-2.7 microm/h) and SPF (7.2+/-1.1, 34.8+/-5.1 h, and 10.1+/-2.5 microm/h). Cell proliferation was no different among the three groups. Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure. These findings indicate that chronic renal failure depresses both the activity of the growth plate cartilage by altering chondrocyte hypertrophy and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more severely lowered than cartilage enlargement and this leads to an accumulation of cartilage at the hypertrophic zone.  (+info)

Measurement of biological activity of somatotropin in hypophysectomized rats. (6/822)

AIM: To develop a method for measurement of biological activity of recombinant DNA-derived somatotropin (rhGH). METHODS: The effects of varying the route, frequency and period of administration of GH, the sex of test animals on the biological responses, body weight gain (BWG), and tibial epiphyseal width (TEW), of hypophysectomized (Hypox) rats were compared, respectively. 4-d BWG, 6-d BWG, and 6-d TEW tests were carried out simultaneously in the same group of Hypox rats to determine the biopotency of GH preparations according to a parallel line bioassay (6-point assay). The final result was chosen from the test which had smaller values for the index of precision (lambda) and the average rate of fiducial limits (ARFL) than other tests. RESULTS: No significant differences in the responses between male and female rats, between sc and im, once daily and twice daily injections of bGH were found. But the BWG and TEW of Hypox rats injected with 0.045 and 0.135 IU.d-1 of bGH for 6 d were significantly greater than that for 4 d. Both 4-d BWG test and 6-d BWG test in the range from 0.020 to 0.500 IU.d-1 had values for lambda = 0.0660 and 0.1747, and for r = 0.9000 and 0.9237, respectively. Three estimates of rhGH preparation compared with the International Standard for somatotropin (IShGH), 4.6132, 3.9829, and 4.8023 IU/ampoule, were obtained separately from 4-d BWG test, 6-d BWG test and 6-d TEW test. And the result from 6-d BWG test was reported finally because it had smaller values for lambda and ARFL (0.0608 and 37.907%) than other two tests. CONCLUSION: Both BWG test and TEW test can be carried out simultaneously in the same group of Hypox rats. 6-d BWG test seemed to be more suitable for potency determination of GH preparations than 4-d BWG test and 6-d TEW test.  (+info)

Immunohistochemical observations on the initial disorders of the epiphyseal growth plate in rats induced by high dose of vitamin A. (7/822)

The initial disorders of the epiphyseal growth plate cartilage were immunohistochemically examined in the proximal tibia of rats administered a high dose of vitamin A. Male Wistar rats were given 100,000 IU/100 g body weight/day of vitamin A for administration periods of 1 to 5 days (Day 1 to 5) from 4 weeks after birth or were given deionized water and used as control. They were sacrificed after 5-bromo-2'-deoxyuridine (BrdU) injection on Day 1 to Day 5 to remove the tibiae. The tibiae were processed for immunohistochemical examinations using antibodies against type I, II, X collagens and BrdU. BrdU-incorporated chondrocytes and type X collagen-negative area were reduced since Day 2 and type X collagen-positive area was reduced since Day 4. The cartilage matrix partially lost type II collagen and deposited type I collagen in the epiphyseal growth plate near the periosteum on Day 5. These findings suggest that a high dose of vitamin A initially disturbed the differentiation from resting to proliferating chondrocytes, subsequently inhibited the differentiation from proliferating to hypertrophic chondrocytes, caused the chondrocytes to deviate from the process of normal differentiation, and finally resulted in the deformation of the epiphyseal growth plate.  (+info)

Cathepsin expression during skeletal development. (8/822)

Cysteine proteinases, cathepsins B, H, K, L and S, have been implicated in several proteolytic processes during development, growth, remodeling and aging, as well as in a variety of pathological processes. For systematic analysis of cathepsin gene expression we have produced cDNA clones for mouse and human cysteine cathepsins. Northern analysis of a panel of total RNAs isolated from 16-19 different human and mouse tissues revealed the presence of mRNAs for cathepsin B, H, K, L and S in most tissues, but each with a distinct profile. Of the different cathepsin mRNAs, those for cathepsin K were clearly the highest in bone and cartilage. However, relatively high mRNA levels for the other cathepsins were also present in these tissues. To better understand the roles of different cathepsins during endochondral ossification in mouse long bones, cathepsin mRNAs were localized by in situ hybridization. Cathepsin K mRNAs were predominantly seen in multinucleated chondroclastic and osteoclastic cells at the osteochondral junction and on the surface of bone spicules. The other cathepsin mRNAs were also seen in osteoclasts, and in hypertrophic and proliferating chondrocytes. These observations were confirmed by immunohistochemistry and suggest that all cysteine cathepsins are involved in matrix degradation during endochondral ossification.  (+info)

A growth plate, also known as an epiphyseal plate or physis, is a layer of cartilaginous tissue found near the ends of long bones in children and adolescents. This region is responsible for the longitudinal growth of bones during development. The growth plate contains actively dividing cells that differentiate into chondrocytes, which produce and deposit new matrix, leading to bone elongation. Once growth is complete, usually in late adolescence or early adulthood, the growth plates ossify (harden) and are replaced by solid bone, transforming into the epiphyseal line.

Chondrocytes are the specialized cells that produce and maintain the extracellular matrix of cartilage tissue. They are responsible for synthesizing and secreting the collagen fibers, proteoglycans, and other components that give cartilage its unique properties, such as elasticity, resiliency, and resistance to compression. Chondrocytes are located within lacunae, or small cavities, in the cartilage matrix, and they receive nutrients and oxygen through diffusion from the surrounding tissue fluid. They are capable of adapting to changes in mechanical stress by modulating the production and organization of the extracellular matrix, which allows cartilage to withstand various loads and maintain its structural integrity. Chondrocytes play a crucial role in the development, maintenance, and repair of cartilaginous tissues throughout the body, including articular cartilage, costal cartilage, and growth plate cartilage.

Bone development, also known as ossification, is the process by which bone tissue is formed and grows. This complex process involves several different types of cells, including osteoblasts, which produce new bone matrix, and osteoclasts, which break down and resorb existing bone tissue.

There are two main types of bone development: intramembranous and endochondral ossification. Intramembranous ossification occurs when bone tissue forms directly from connective tissue, while endochondral ossification involves the formation of a cartilage model that is later replaced by bone.

During fetal development, most bones develop through endochondral ossification, starting as a cartilage template that is gradually replaced by bone tissue. However, some bones, such as those in the skull and clavicles, develop through intramembranous ossification.

Bone development continues after birth, with new bone tissue being laid down and existing tissue being remodeled throughout life. This ongoing process helps to maintain the strength and integrity of the skeleton, allowing it to adapt to changing mechanical forces and repair any damage that may occur.

The epiphyses are the rounded ends of long bones in the body, which articulate with other bones to form joints. They are separated from the main shaft of the bone (diaphysis) by a growth plate called the physis or epiphyseal plate. The epiphyses are made up of spongy bone and covered with articular cartilage, which allows for smooth movement between bones. During growth, the epiphyseal plates produce new bone cells that cause the bone to lengthen until they eventually fuse during adulthood, at which point growth stops.

The tibia, also known as the shin bone, is the larger of the two bones in the lower leg and part of the knee joint. It supports most of the body's weight and is a major insertion point for muscles that flex the foot and bend the leg. The tibia articulates with the femur at the knee joint and with the fibula and talus bone at the ankle joint. Injuries to the tibia, such as fractures, are common in sports and other activities that put stress on the lower leg.

Cartilage is a type of connective tissue that is found throughout the body in various forms. It is made up of specialized cells called chondrocytes, which are embedded in a firm, flexible matrix composed of collagen fibers and proteoglycans. This unique structure gives cartilage its characteristic properties of being both strong and flexible.

There are three main types of cartilage in the human body: hyaline cartilage, elastic cartilage, and fibrocartilage.

1. Hyaline cartilage is the most common type and is found in areas such as the articular surfaces of bones (where they meet to form joints), the nose, trachea, and larynx. It has a smooth, glassy appearance and provides a smooth, lubricated surface for joint movement.
2. Elastic cartilage contains more elastin fibers than hyaline cartilage, which gives it greater flexibility and resilience. It is found in structures such as the external ear and parts of the larynx and epiglottis.
3. Fibrocartilage has a higher proportion of collagen fibers and fewer chondrocytes than hyaline or elastic cartilage. It is found in areas that require high tensile strength, such as the intervertebral discs, menisci (found in joints like the knee), and the pubic symphysis.

Cartilage plays a crucial role in supporting and protecting various structures within the body, allowing for smooth movement and providing a cushion between bones to absorb shock and prevent wear and tear. However, cartilage has limited capacity for self-repair and regeneration, making damage or degeneration of cartilage tissue a significant concern in conditions such as osteoarthritis.

Bone plates are medical devices used in orthopedic surgery to stabilize and hold together fractured or broken bones during the healing process. They are typically made of surgical-grade stainless steel, titanium, or other biocompatible materials. The plate is shaped to fit the contour of the bone and is held in place with screws that are inserted through the plate and into the bone on either side of the fracture. This provides stability and alignment to the broken bones, allowing them to heal properly. Bone plates can be used to treat a variety of fractures, including those that are complex or unstable. After healing is complete, the bone plate may be left in place or removed, depending on the individual's needs and the surgeon's recommendation.

Osteochondrodysplasias are a group of genetic disorders that affect the development of bones and cartilage. These conditions can result in dwarfism or short stature, as well as other skeletal abnormalities. Osteochondrodysplasias can be caused by mutations in genes that regulate bone and cartilage growth, and they are often characterized by abnormalities in the shape, size, and/or structure of the bones and cartilage.

There are many different types of osteochondrodysplasias, each with its own specific symptoms and patterns of inheritance. Some common examples include achondroplasia, thanatophoric dysplasia, and spondyloepiphyseal dysplasia. These conditions can vary in severity, and some may be associated with other health problems, such as respiratory difficulties or neurological issues.

Treatment for osteochondrodysplasias typically focuses on managing the symptoms and addressing any related health concerns. This may involve physical therapy, bracing or surgery to correct skeletal abnormalities, and treatment for any associated medical conditions. In some cases, genetic counseling may also be recommended for individuals with osteochondrodysplasias and their families.

The metatarsal bones are a group of five long bones in the foot that connect the tarsal bones in the hindfoot to the phalanges in the forefoot. They are located between the tarsal and phalangeal bones and are responsible for forming the arch of the foot and transmitting weight-bearing forces during walking and running. The metatarsal bones are numbered 1 to 5, with the first metatarsal being the shortest and thickest, and the fifth metatarsal being the longest and thinnest. Each metatarsal bone has a base, shaft, and head, and they articulate with each other and with the surrounding bones through joints. Any injury or disorder affecting the metatarsal bones can cause pain and difficulty in walking or standing.

Collagen type X is a specific type of collagen that is primarily found in the hypertrophic zone of mature cartilage, which is located near the site of bone formation during endochondral ossification. It plays a crucial role in the mineralization process of the cartilage matrix and is essential for the formation of healthy bones. Collagen type X is composed of three identical alpha chains that form a triple helix structure, and it is synthesized by chondrocytes, which are the specialized cells found in cartilage tissue. Mutations in the gene that encodes collagen type X have been associated with certain skeletal disorders, such as Schmid metaphyseal chondrodysplasia.

Chondrogenesis is the process of cartilage formation during embryonic development and in the healing of certain types of injuries. It involves the differentiation of mesenchymal stem cells into chondrocytes, which are the specialized cells that produce and maintain the extracellular matrix of cartilage.

During chondrogenesis, the mesenchymal stem cells condense and form a template for the future cartilaginous tissue. These cells then differentiate into chondrocytes, which begin to produce and deposit collagen type II, proteoglycans, and other extracellular matrix components that give cartilage its unique biochemical and mechanical properties.

Chondrogenesis is a critical process for the development of various structures in the body, including the skeletal system, where it plays a role in the formation of articular cartilage, growth plates, and other types of cartilage. Understanding the molecular mechanisms that regulate chondrogenesis is important for developing therapies to treat cartilage injuries and degenerative diseases such as osteoarthritis.

Physiologic calcification is the normal deposit of calcium salts in body tissues and organs. It is a natural process that occurs as part of the growth and development of the human body, as well as during the repair and remodeling of tissues.

Calcium is an essential mineral that plays a critical role in many bodily functions, including bone formation, muscle contraction, nerve impulse transmission, and blood clotting. In order to maintain proper levels of calcium in the body, excess calcium that is not needed for these functions may be deposited in various tissues as a normal part of the aging process.

Physiologic calcification typically occurs in areas such as the walls of blood vessels, the lungs, and the heart valves. While these calcifications are generally harmless, they can sometimes lead to complications, particularly if they occur in large amounts or in sensitive areas. For example, calcification of the coronary arteries can increase the risk of heart disease, while calcification of the lung tissue can cause respiratory symptoms.

It is important to note that pathologic calcification, on the other hand, refers to the abnormal deposit of calcium salts in tissues and organs, which can be caused by various medical conditions such as chronic kidney disease, hyperparathyroidism, and certain infections. Pathologic calcification is not a normal process and can lead to serious health complications if left untreated.

"Bone" is the hard, dense connective tissue that makes up the skeleton of vertebrate animals. It provides support and protection for the body's internal organs, and serves as a attachment site for muscles, tendons, and ligaments. Bone is composed of cells called osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively, and an extracellular matrix made up of collagen fibers and mineral crystals.

Bones can be classified into two main types: compact bone and spongy bone. Compact bone is dense and hard, and makes up the outer layer of all bones and the shafts of long bones. Spongy bone is less dense and contains large spaces, and makes up the ends of long bones and the interior of flat and irregular bones.

The human body has 206 bones in total. They can be further classified into five categories based on their shape: long bones, short bones, flat bones, irregular bones, and sesamoid bones.

Osteogenesis is the process of bone formation or development. It involves the differentiation and maturation of osteoblasts, which are bone-forming cells that synthesize and deposit the organic matrix of bone tissue, composed mainly of type I collagen. This organic matrix later mineralizes to form the inorganic crystalline component of bone, primarily hydroxyapatite.

There are two primary types of osteogenesis: intramembranous and endochondral. Intramembranous osteogenesis occurs directly within connective tissue, where mesenchymal stem cells differentiate into osteoblasts and form bone tissue without an intervening cartilage template. This process is responsible for the formation of flat bones like the skull and clavicles.

Endochondral osteogenesis, on the other hand, involves the initial development of a cartilaginous model or template, which is later replaced by bone tissue. This process forms long bones, such as those in the limbs, and occurs through several stages involving chondrocyte proliferation, hypertrophy, and calcification, followed by invasion of blood vessels and osteoblasts to replace the cartilage with bone tissue.

Abnormalities in osteogenesis can lead to various skeletal disorders and diseases, such as osteogenesis imperfecta (brittle bone disease), achondroplasia (a form of dwarfism), and cleidocranial dysplasia (a disorder affecting skull and collarbone development).

Thiram is not typically considered a medical term, but it is a chemical compound that has been used in some medical and healthcare settings. Thiram is an organic compound that belongs to the class of chemicals known as dithiocarbamates. It is primarily used as a fungicide to prevent fungal growth on crops such as potatoes, beans, and nuts.

In medical contexts, thiram has been used in some topical creams and ointments as an antifungal agent to treat skin conditions like athlete's foot and ringworm. However, its use in medicine is relatively limited due to concerns about its potential toxicity and environmental impact.

It is important to note that the use of thiram in topical medications has declined over time, and it is not commonly used in modern medical practice. Always consult with a healthcare professional for accurate information regarding medical treatments and therapies.

The metacarpus is the medical term for the part of the hand located between the carpus (wrist) and the digits (fingers). It consists of five bones, known as the metacarpal bones, which are numbered 1 to 5 from the thumb side to the little finger side. Each metacarpal bone has a base, a shaft, and a head. The bases of the metacarpal bones articulate with the carpal bones to form the wrist joint, while the heads of the metacarpal bones form the knuckles at the back of the hand.

The metacarpus plays an essential role in hand function as it provides stability and support for the movement of the fingers and thumb. Injuries or conditions affecting the metacarpus can significantly impact hand function, causing pain, stiffness, weakness, or deformity.

The femur is the medical term for the thigh bone, which is the longest and strongest bone in the human body. It connects the hip bone to the knee joint and plays a crucial role in supporting the weight of the body and allowing movement during activities such as walking, running, and jumping. The femur is composed of a rounded head, a long shaft, and two condyles at the lower end that articulate with the tibia and patella to form the knee joint.

Growth Differentiation Factor 10 (GDF10), also known as Bone Morphogenetic Protein 3b (BMP3b), is a member of the Transforming Growth Factor-β (TGF-β) superfamily. It is a secreted signaling protein that plays crucial roles in various biological processes, including embryonic development, tissue homeostasis, and repair. Specifically, GDF10 has been implicated in regulating skeletal growth, joint formation, and neural crest cell migration during embryogenesis. In addition, it is involved in the regulation of bone mass, as well as the maintenance and differentiation of mesenchymal stem cells. Dysregulation of GDF10 has been associated with several pathological conditions, such as skeletal disorders and tumorigenesis.

Hypertrophy, in the context of physiology and pathology, refers to an increase in the size of an organ or tissue due to an enlargement of its constituent cells. It is often used to describe the growth of muscle cells (myocytes) in response to increased workload or hormonal stimulation, resulting in an increase in muscle mass. However, hypertrophy can also occur in other organs such as the heart (cardiac hypertrophy) in response to high blood pressure or valvular heart disease.

It is important to note that while hypertrophy involves an increase in cell size, hyperplasia refers to an increase in cell number. In some cases, both hypertrophy and hyperplasia can occur together, leading to a significant increase in the overall size and function of the organ or tissue.

Parathyroid Hormone-Related Protein (PTHrP) is a protein that is encoded by the PTHLH gene in humans. It is structurally similar to parathyroid hormone (PTH) and was initially identified due to its role in humoral hypercalcemia of malignancy, a condition characterized by high levels of calcium in the blood caused by certain types of cancer.

PTHrP has a variety of functions in the body, including regulation of calcium and phosphate homeostasis, cell growth and differentiation, and bone metabolism. It acts through a specific G protein-coupled receptor called the PTH/PTHrP receptor, which is found in many tissues throughout the body, including bone, kidney, and cartilage.

In contrast to PTH, which is primarily produced by the parathyroid glands and regulates calcium levels in the blood, PTHrP is produced by many different types of cells throughout the body. Its expression is regulated in a tissue-specific manner, and its functions can vary depending on the context in which it is produced.

Overall, PTHrP plays important roles in normal physiology as well as in various disease states, including cancer, bone disorders, and developmental abnormalities.

Developmental bone diseases are a group of medical conditions that affect the growth and development of bones. These diseases are present at birth or develop during childhood and adolescence, when bones are growing rapidly. They can result from genetic mutations, hormonal imbalances, or environmental factors such as poor nutrition.

Some examples of developmental bone diseases include:

1. Osteogenesis imperfecta (OI): Also known as brittle bone disease, OI is a genetic disorder that affects the body's production of collagen, a protein necessary for healthy bones. People with OI have fragile bones that break easily and may also experience other symptoms such as blue sclerae (whites of the eyes), hearing loss, and joint laxity.
2. Achondroplasia: This is the most common form of dwarfism, caused by a genetic mutation that affects bone growth. People with achondroplasia have short limbs and a large head relative to their body size.
3. Rickets: A condition caused by vitamin D deficiency or an inability to absorb or use vitamin D properly. This leads to weak, soft bones that can bow or bend easily, particularly in children.
4. Fibrous dysplasia: A rare bone disorder where normal bone is replaced with fibrous tissue, leading to weakened bones and deformities.
5. Scoliosis: An abnormal curvature of the spine that can develop during childhood or adolescence. While not strictly a developmental bone disease, scoliosis can be caused by various underlying conditions such as cerebral palsy, muscular dystrophy, or spina bifida.

Treatment for developmental bone diseases varies depending on the specific condition and its severity. Treatment may include medication, physical therapy, bracing, or surgery to correct deformities and improve function. Regular follow-up with a healthcare provider is essential to monitor growth, manage symptoms, and prevent complications.

Fibroblast Growth Factor Receptor 3 (FGFR3) is a type of cell surface receptor that binds to fibroblast growth factors (FGFs), which are signaling proteins involved in various biological processes such as cell division, growth, and wound healing.

FGFR3 is a transmembrane protein with an extracellular domain that contains the binding site for FGFs, a transmembrane domain, and an intracellular tyrosine kinase domain that activates downstream signaling pathways upon FGF binding.

Mutations in the FGFR3 gene have been associated with several human genetic disorders, including thanatophoric dysplasia, achondroplasia, and hypochondroplasia, which are characterized by abnormal bone growth and development. In these conditions, gain-of-function mutations in FGFR3 lead to increased receptor activity and activation of downstream signaling pathways, resulting in impaired endochondral ossification and short-limbed dwarfism.

In addition to its role in bone growth and development, FGFR3 has been implicated in the regulation of cell proliferation, differentiation, and survival in various tissues, including the brain, lung, and kidney. Dysregulation of FGFR3 signaling has also been associated with cancer, including bladder, breast, and cervical cancers.

A skeleton is not a medical condition or term, but rather an anatomical structure. Medically, the skeletal system refers to the body's organic framework that provides support and shape to the body, protects vital organs, and enables motion through attachment to muscles. The human skeleton is made up of 206 bones in an adult, which are categorized into axial (80 bones) and appendicular (126 bones) skeletons.

The axial skeleton forms the central axis of the body and consists of the skull, vertebral column, sternum, and ribcage. The appendicular skeleton includes the upper and lower extremities (limbs), shoulder girdle, and pelvic girdle.

In summary, a skeleton is the collective term for all bones in an organism's body that provide structure, support, protection, and mobility.

Dwarfism is a medical condition that is characterized by short stature, typically with an adult height of 4 feet 10 inches (147 centimeters) or less. It is caused by a variety of genetic and medical conditions that affect bone growth, including skeletal dysplasias, hormonal deficiencies, and chromosomal abnormalities.

Skeletal dysplasias are the most common cause of dwarfism and are characterized by abnormalities in the development and growth of bones and cartilage. Achondroplasia is the most common form of skeletal dysplasia, accounting for about 70% of all cases of dwarfism. It is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene and results in short limbs, a large head, and a prominent forehead.

Hormonal deficiencies, such as growth hormone deficiency or hypothyroidism, can also cause dwarfism if they are not diagnosed and treated early. Chromosomal abnormalities, such as Turner syndrome (monosomy X) or Down syndrome (trisomy 21), can also result in short stature and other features of dwarfism.

It is important to note that people with dwarfism are not "dwarves" - the term "dwarf" is a medical and sociological term used to describe individuals with this condition, while "dwarves" is a term often used in fantasy literature and media to refer to mythical beings. The use of the term "dwarf" can be considered disrespectful or offensive to some people with dwarfism, so it is important to use respectful language when referring to individuals with this condition.

Hedgehog proteins are a group of signaling molecules that play crucial roles in the development and regulation of various biological processes in animals. They are named after the hedgehog mutant fruit flies, which have spiky bristles due to defects in this pathway. These proteins are involved in cell growth, differentiation, and tissue regeneration. They exert their effects by binding to specific receptors on the surface of target cells, leading to a cascade of intracellular signaling events that ultimately influence gene expression and cell behavior.

There are three main types of Hedgehog proteins in mammals: Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). These protecules undergo post-translational modifications, including cleavage and lipid modification, which are essential for their activity. Dysregulation of Hedgehog signaling has been implicated in various diseases, including cancer, developmental abnormalities, and degenerative disorders.

In medical terms, ribs are the long, curved bones that make up the ribcage in the human body. They articulate with the thoracic vertebrae posteriorly and connect to the sternum anteriorly via costal cartilages. There are 12 pairs of ribs in total, and they play a crucial role in protecting the lungs and heart, allowing room for expansion and contraction during breathing. Ribs also provide attachment points for various muscles involved in respiration and posture.

SOXD (SRY-related HMG box gene D) transcription factors are a subgroup of the SOX family of proteins that regulate gene expression during development and differentiation. The SOXD group includes two closely related members, SOX5 and SOX6, which contain a highly conserved HMG (high mobility group) DNA-binding domain. These transcription factors play crucial roles in various biological processes, such as chondrogenesis, neurogenesis, and spermatogenesis, by binding to specific DNA sequences and regulating the transcription of target genes. SOX5 and SOX6 can form heterodimers or homodimers and interact with other transcription factors and cofactors to modulate their activities, contributing to the precise control of gene expression during development.

Achondroplasia is a genetic disorder that affects bone growth, leading to dwarfism. It is the most common form of short-limbed dwarfism and is caused by a mutation in the FGFR3 gene. This mutation results in impaired endochondral ossification, which is the process by which cartilage is converted into bone.

People with achondroplasia have a characteristic appearance, including:

* Short stature (typically less than 4 feet, 4 inches tall)
* Disproportionately short arms and legs
* Large head with a prominent forehead and flat nasal bridge
* Short fingers with a gap between the middle and ring fingers (known as a trident hand)
* Bowing of the lower legs
* A swayed back (lordosis)

Achondroplasia is usually inherited in an autosomal dominant manner, which means that a child has a 50% chance of inheriting the disorder if one parent has it. However, about 80% of cases result from new mutations in the FGFR3 gene and occur in people with no family history of the condition.

While achondroplasia can cause various medical issues, such as breathing difficulties, ear infections, and spinal cord compression, most individuals with this condition have normal intelligence and a typical lifespan. Treatment typically focuses on managing specific symptoms and addressing any related complications.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Parathyroid Hormone Receptor Type 1 (PTH1R) is a type of G protein-coupled receptor that binds to parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP). It is primarily found in bone and kidney cells.

The activation of PTH1R by PTH or PTHrP leads to a series of intracellular signaling events that regulate calcium homeostasis, bone metabolism, and renal function. In the bone, PTH1R stimulates the release of calcium from bone matrix into the bloodstream, while in the kidney, it increases the reabsorption of calcium in the distal tubule and inhibits phosphate reabsorption.

Mutations in the gene encoding PTH1R can lead to several genetic disorders, such as Blomstrand chondrodysplasia, Jansen metaphyseal chondrodysplasia, and hypoparathyroidism type 1B. These conditions are characterized by abnormalities in bone development, growth, and mineralization.

Multiple hereditary exostoses (MHE) is a genetic condition characterized by the growth of multiple benign tumors known as osteochondromas. These tumors typically develop at the ends of long bones near the growth plates and can cause various skeletal deformities, limitations in mobility, and other health issues.

MHE is usually inherited in an autosomal dominant pattern, meaning that a child has a 50% chance of inheriting the condition if one parent has it. However, some cases may result from spontaneous mutations. The condition typically becomes apparent during childhood or adolescence and can affect both sexes equally.

The primary diagnostic feature of MHE is the presence of multiple osteochondromas, which are made up of bone and cartilage. These growths can cause a range of symptoms, including pain, swelling, decreased mobility, and an increased risk of fractures. In some cases, they may also lead to complications such as nerve compression or vascular damage.

Treatment for MHE typically involves surgical removal of the osteochondromas, particularly if they are causing significant symptoms or complications. Regular monitoring is also important to detect any new growths and assess their potential impact on health. In addition, physical therapy and other supportive measures may be recommended to help manage symptoms and maintain mobility.

Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints. It provides a cushion between bones and allows for smooth movement by reducing friction. Articular cartilage also absorbs shock and distributes loads evenly across the joint, protecting the bones from damage. It is avascular, meaning it does not have its own blood supply, and relies on the surrounding synovial fluid for nutrients. Over time, articular cartilage can wear down or become damaged due to injury or disease, leading to conditions such as osteoarthritis.

Osteochondritis is a joint condition where a piece of cartilage or bone in the joint separates from its attachment due to a lack of blood supply. This can cause pain, stiffness, and potentially restricted movement in the affected joint. It often occurs in weight-bearing joints like the knee or ankle, and is more common in children and adolescents. The separated piece may sometimes float around in the joint space, causing further damage to the cartilage and bone. If left untreated, it can lead to long-term joint problems. Also known as osteochondrosis or osteochondritis dissecans.

In situ hybridization (ISH) is a molecular biology technique used to detect and localize specific nucleic acid sequences, such as DNA or RNA, within cells or tissues. This technique involves the use of a labeled probe that is complementary to the target nucleic acid sequence. The probe can be labeled with various types of markers, including radioisotopes, fluorescent dyes, or enzymes.

During the ISH procedure, the labeled probe is hybridized to the target nucleic acid sequence in situ, meaning that the hybridization occurs within the intact cells or tissues. After washing away unbound probe, the location of the labeled probe can be visualized using various methods depending on the type of label used.

In situ hybridization has a wide range of applications in both research and diagnostic settings, including the detection of gene expression patterns, identification of viral infections, and diagnosis of genetic disorders.

Bone matrix refers to the non-cellular component of bone that provides structural support and functions as a reservoir for minerals, such as calcium and phosphate. It is made up of organic and inorganic components. The organic component consists mainly of type I collagen fibers, which provide flexibility and tensile strength to the bone. The inorganic component is primarily composed of hydroxyapatite crystals, which give bone its hardness and compressive strength. Bone matrix also contains other proteins, growth factors, and signaling molecules that regulate bone formation, remodeling, and repair.

The humerus is the long bone in the upper arm that extends from the shoulder joint (glenohumeral joint) to the elbow joint. It articulates with the glenoid cavity of the scapula to form the shoulder joint and with the radius and ulna bones at the elbow joint. The proximal end of the humerus has a rounded head that provides for movement in multiple planes, making it one of the most mobile joints in the body. The greater and lesser tubercles are bony prominences on the humeral head that serve as attachment sites for muscles that move the shoulder and arm. The narrow shaft of the humerus provides stability and strength for weight-bearing activities, while the distal end forms two articulations: one with the ulna (trochlea) and one with the radius (capitulum). Together, these structures allow for a wide range of motion in the shoulder and elbow joints.

Collagen Type II is a specific type of collagen that is a major component of the extracellular matrix in articular cartilage, which is the connective tissue that covers and protects the ends of bones in joints. It is also found in other tissues such as the vitreous humor of the eye and the inner ear.

Collagen Type II is a triple helix molecule composed of three polypeptide chains that contain a high proportion of the amino acids proline and hydroxyproline. This type of collagen provides structural support and elasticity to tissues, and it also plays a role in the regulation of cell behavior and signaling.

Collagen Type II is a target for autoimmune responses in conditions such as rheumatoid arthritis, where the immune system mistakenly attacks the body's own collagen, leading to joint inflammation and damage. It is also a common component of various dietary supplements and therapies used to support joint health and treat osteoarthritis.

The neural plate is a structure formed during the embryonic development of vertebrates. It is a thickened plate of ectodermal cells located on the dorsal surface of the developing embryo. The neural plate gives rise to the central nervous system, including the brain and spinal cord.

The process of neural plate formation begins with the specification of ectodermal cells into neural fated cells, a process that is regulated by various signaling molecules. Once specified, these cells undergo morphological changes, resulting in the thickening of the ectoderm to form the neural plate.

The neural plate then undergoes a series of folding movements, leading to the formation of the neural tube, which eventually develops into the brain and spinal cord. The edges of the neural plate, known as the neural folds, come together and fuse, forming a closed tube. Failure of the neural folds to fuse properly can result in neural tube defects, such as spina bifida.

Overall, the neural plate is a critical structure in the development of the nervous system in vertebrates, and its formation and subsequent development are tightly regulated by various genetic and environmental factors.

Hyperostosis is a medical term that refers to an excessive growth or abnormal thickening of bone tissue. It can occur as a result of various conditions, such as inflammation, injury, or genetic disorders. The extra bone growth can cause pain, stiffness, and limited mobility in the affected area. In some cases, hyperostosis can also lead to deformities and other complications.

There are several types of hyperostosis, including:

1. Diffuse idiopathic skeletal hyperostosis (DISH): This is a condition that affects the spine, causing calcification and stiffening of the ligaments and bone spurs to form along the edges of the vertebrae. It is often asymptomatic but can cause pain and stiffness in some cases.
2. Flat bone hyperostosis: This type of hyperostosis affects the flat bones of the body, such as the skull, ribs, and pelvis. It can be caused by various conditions, including Paget's disease, fibrous dysplasia, and certain types of cancer.
3. Focal hyperostosis: This refers to localized areas of bone overgrowth that can occur in response to injury, infection, or inflammation. Examples include heterotopic ossification (the formation of bone in soft tissues) and Freiberg's infarction (a condition that affects the joint surface of the metatarsal bones in the foot).
4. Hyperostosis frontalis interna: This is a benign condition that causes thickening of the inner table of the frontal bone in the skull. It is more common in women and often asymptomatic but can cause headaches and other symptoms in some cases.

Treatment for hyperostosis depends on the underlying cause and severity of the condition. In some cases, no treatment may be necessary. However, if the condition causes pain or limits mobility, various treatments may be recommended, such as medication, physical therapy, or surgery.

The periosteum is a highly vascularized and innervated tissue that surrounds the outer surface of bones, except at the articular surfaces. It consists of two layers: an outer fibrous layer containing blood vessels, nerves, and fibroblasts; and an inner cellular layer called the cambium or osteogenic layer, which contains progenitor cells capable of bone formation and repair.

The periosteum plays a crucial role in bone growth, remodeling, and healing by providing a source of osteoprogenitor cells and blood supply. It also contributes to the sensation of pain in response to injury or inflammation of the bone. Additionally, the periosteum can respond to mechanical stress by activating bone formation, making it an essential component in orthopedic treatments such as distraction osteogenesis.

Rickets is a medical condition characterized by the softening and weakening of bones in children, primarily caused by deficiency of vitamin D, calcium, or phosphate. It leads to skeletal deformities, bone pain, and growth retardation. Prolonged lack of sunlight exposure, inadequate intake of vitamin D-rich foods, or impaired absorption or utilization of vitamin D can contribute to the development of rickets.

Growth disorders are medical conditions that affect a person's growth and development, leading to shorter or taller stature than expected for their age, sex, and ethnic group. These disorders can be caused by various factors, including genetic abnormalities, hormonal imbalances, chronic illnesses, malnutrition, and psychosocial issues.

There are two main types of growth disorders:

1. Short stature: This refers to a height that is significantly below average for a person's age, sex, and ethnic group. Short stature can be caused by various factors, including genetic conditions such as Turner syndrome or dwarfism, hormonal deficiencies, chronic illnesses, malnutrition, and psychosocial issues.
2. Tall stature: This refers to a height that is significantly above average for a person's age, sex, and ethnic group. Tall stature can be caused by various factors, including genetic conditions such as Marfan syndrome or Klinefelter syndrome, hormonal imbalances, and certain medical conditions like acromegaly.

Growth disorders can have significant impacts on a person's physical, emotional, and social well-being. Therefore, it is essential to diagnose and manage these conditions early to optimize growth and development and improve overall quality of life. Treatment options for growth disorders may include medication, nutrition therapy, surgery, or a combination of these approaches.

Developmental gene expression regulation refers to the processes that control the activation or repression of specific genes during embryonic and fetal development. These regulatory mechanisms ensure that genes are expressed at the right time, in the right cells, and at appropriate levels to guide proper growth, differentiation, and morphogenesis of an organism.

Developmental gene expression regulation is a complex and dynamic process involving various molecular players, such as transcription factors, chromatin modifiers, non-coding RNAs, and signaling molecules. These regulators can interact with cis-regulatory elements, like enhancers and promoters, to fine-tune the spatiotemporal patterns of gene expression during development.

Dysregulation of developmental gene expression can lead to various congenital disorders and developmental abnormalities. Therefore, understanding the principles and mechanisms governing developmental gene expression regulation is crucial for uncovering the etiology of developmental diseases and devising potential therapeutic strategies.

Aggrecan is a large, complex proteoglycan molecule found in the extracellular matrix of articular cartilage and other connective tissues. It is a key component of the structural framework of these tissues, helping to provide resiliency, cushioning, and protection to the cells within. Aggrecan contains numerous glycosaminoglycan (GAG) chains, which are negatively charged molecules that attract water and ions, creating a swelling pressure that contributes to the tissue's load-bearing capacity.

The medical definition of 'Aggrecans' can be described as:

1. A large proteoglycan molecule found in articular cartilage and other connective tissues.
2. Composed of a core protein with attached glycosaminoglycan (GAG) chains, primarily chondroitin sulfate and keratan sulfate.
3. Plays a crucial role in the biomechanical properties of articular cartilage by attracting water and ions, creating a swelling pressure that contributes to the tissue's load-bearing capacity.
4. Aggrecan degradation or loss is associated with various joint diseases, such as osteoarthritis, due to reduced structural integrity and shock-absorbing capabilities of articular cartilage.

Osteoblasts are specialized bone-forming cells that are derived from mesenchymal stem cells. They play a crucial role in the process of bone formation and remodeling. Osteoblasts synthesize, secrete, and mineralize the organic matrix of bones, which is mainly composed of type I collagen.

These cells have receptors for various hormones and growth factors that regulate their activity, such as parathyroid hormone, vitamin D, and transforming growth factor-beta. When osteoblasts are not actively producing bone matrix, they can become trapped within the matrix they produce, where they differentiate into osteocytes, which are mature bone cells that play a role in maintaining bone structure and responding to mechanical stress.

Abnormalities in osteoblast function can lead to various bone diseases, such as osteoporosis, osteogenesis imperfecta, and Paget's disease of bone.

Collagen is the most abundant protein in the human body, and it is a major component of connective tissues such as tendons, ligaments, skin, and bones. Collagen provides structure and strength to these tissues and helps them to withstand stretching and tension. It is made up of long chains of amino acids, primarily glycine, proline, and hydroxyproline, which are arranged in a triple helix structure. There are at least 16 different types of collagen found in the body, each with slightly different structures and functions. Collagen is important for maintaining the integrity and health of tissues throughout the body, and it has been studied for its potential therapeutic uses in various medical conditions.

Heterotopic ossification (HO) is a medical condition where bone tissue forms outside the skeleton, in locations where it does not typically exist. This process can occur in various soft tissues, such as muscles, tendons, ligaments, or even inside joint capsules. The abnormal bone growth can lead to pain, stiffness, limited range of motion, and, in some cases, loss of function in the affected area.

There are several types of heterotopic ossification, including:

1. Myositis ossificans - This form is often associated with trauma or injury, such as muscle damage from a fracture, surgery, or direct blow. It typically affects young, active individuals and usually resolves on its own within months to a few years.
2. Neurogenic heterotopic ossification (NHO) - Also known as "traumatic heterotopic ossification," this form is often linked to spinal cord injuries, brain injuries, or central nervous system damage. NHO can cause significant impairment and may require surgical intervention in some cases.
3. Fibrodysplasia ossificans progressiva (FOP) - This rare, genetic disorder causes progressive heterotopic ossification throughout the body, starting in early childhood. The condition significantly impacts mobility and quality of life, with no known cure.

The exact mechanisms behind heterotopic ossification are not fully understood, but it is believed that a combination of factors, including inflammation, tissue injury, and genetic predisposition, contribute to its development. Treatment options may include nonsteroidal anti-inflammatory drugs (NSAIDs), radiation therapy, physical therapy, or surgical removal of the abnormal bone growth, depending on the severity and location of the HO.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

Alkaline phosphatase (ALP) is an enzyme found in various body tissues, including the liver, bile ducts, digestive system, bones, and kidneys. It plays a role in breaking down proteins and minerals, such as phosphate, in the body.

The medical definition of alkaline phosphatase refers to its function as a hydrolase enzyme that removes phosphate groups from molecules at an alkaline pH level. In clinical settings, ALP is often measured through blood tests as a biomarker for various health conditions.

Elevated levels of ALP in the blood may indicate liver or bone diseases, such as hepatitis, cirrhosis, bone fractures, or cancer. Therefore, physicians may order an alkaline phosphatase test to help diagnose and monitor these conditions. However, it is essential to interpret ALP results in conjunction with other diagnostic tests and clinical findings for accurate diagnosis and treatment.

Insulin-like growth factor I (IGF-I) is a hormone that plays a crucial role in growth and development. It is a small protein with structural and functional similarity to insulin, hence the name "insulin-like." IGF-I is primarily produced in the liver under the regulation of growth hormone (GH).

IGF-I binds to its specific receptor, the IGF-1 receptor, which is widely expressed throughout the body. This binding activates a signaling cascade that promotes cell proliferation, differentiation, and survival. In addition, IGF-I has anabolic effects on various tissues, including muscle, bone, and cartilage, contributing to their growth and maintenance.

IGF-I is essential for normal growth during childhood and adolescence, and it continues to play a role in maintaining tissue homeostasis throughout adulthood. Abnormal levels of IGF-I have been associated with various medical conditions, such as growth disorders, diabetes, and certain types of cancer.

The femoral head is the rounded, ball-like top portion of the femur (thigh bone) that fits into the hip socket (acetabulum) to form the hip joint. It has a smooth, articular cartilage surface that allows for smooth and stable articulation with the pelvis. The femoral head is connected to the femoral neck, which is a narrower section of bone that angles downward and leads into the shaft of the femur. Together, the femoral head and neck provide stability and range of motion to the hip joint.

Extracellular matrix (ECM) proteins are a group of structural and functional molecules that provide support, organization, and regulation to the cells in tissues and organs. The ECM is composed of a complex network of proteins, glycoproteins, and carbohydrates that are secreted by the cells and deposited outside of them.

ECM proteins can be classified into several categories based on their structure and function, including:

1. Collagens: These are the most abundant ECM proteins and provide strength and stability to tissues. They form fibrils that can withstand high tensile forces.
2. Proteoglycans: These are complex molecules made up of a core protein and one or more glycosaminoglycan (GAG) chains. The GAG chains attract water, making proteoglycans important for maintaining tissue hydration and resilience.
3. Elastin: This is an elastic protein that allows tissues to stretch and recoil, such as in the lungs and blood vessels.
4. Fibronectins: These are large glycoproteins that bind to cells and ECM components, providing adhesion, migration, and signaling functions.
5. Laminins: These are large proteins found in basement membranes, which provide structural support for epithelial and endothelial cells.
6. Tenascins: These are large glycoproteins that modulate cell adhesion and migration, and regulate ECM assembly and remodeling.

Together, these ECM proteins create a microenvironment that influences cell behavior, differentiation, and function. Dysregulation of ECM proteins has been implicated in various diseases, including fibrosis, cancer, and degenerative disorders.

Core Binding Factor Alpha 1 Subunit, also known as CBF-A1 or RUNX1, is a protein that plays a crucial role in hematopoiesis, which is the process of blood cell development. It is a member of the core binding factor (CBF) complex, which regulates gene transcription and is essential for the differentiation and maturation of hematopoietic stem cells into mature blood cells.

The CBF complex consists of three subunits: CBF-A, CBF-B, and a histone deacetylase (HDAC). The CBF-A subunit can have several isoforms, including CBF-A1, which is encoded by the RUNX1 gene. Mutations in the RUNX1 gene have been associated with various hematological disorders, such as acute myeloid leukemia (AML), familial platelet disorder with propensity to develop AML, and thrombocytopenia with absent radii syndrome.

CBF-A1/RUNX1 functions as a transcription factor that binds to DNA at specific sequences called core binding factors, thereby regulating the expression of target genes involved in hematopoiesis. Proper regulation of these genes is essential for normal blood cell development and homeostasis.

Matrilin proteins are a group of extracellular matrix (ECM) proteins that are predominantly found in cartilaginous tissues, such as articular cartilage, costal cartilage, and intervertebral discs. They belong to the von Willebrand factor A (vWF-A) domain-containing protein family and play important roles in maintaining the structural integrity and organization of the ECM.

Matrilin proteins are composed of multiple domains, including vWF-A domains, coiled-coil domains, and calcium-binding epidermal growth factor (cbEGF)-like domains. They can form multimeric complexes through their coiled-coil domains, which helps to stabilize the ECM network.

There are four known matrilin proteins in humans, designated as Matrilin-1, Matrilin-2, Matrilin-3, and Matrilin-4. Each of these proteins has distinct tissue distribution patterns and functions. For example, Matrilin-1 is primarily found in hyaline cartilage and is involved in regulating chondrocyte differentiation and matrix assembly. Matrilin-2 is widely expressed in various tissues, including cartilage, tendon, and ligament, and plays a role in maintaining the organization of collagen fibrils. Matrilin-3 is specifically expressed in articular cartilage and is involved in regulating the formation and maintenance of the cartilaginous matrix. Matrilin-4 is found in both hyaline and fibrocartilage, as well as in tendons and ligaments, and has been implicated in regulating collagen fibrillogenesis and tissue development.

Mutations in matrilin genes have been associated with various musculoskeletal disorders, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). These genetic defects can lead to abnormalities in the structure and organization of the ECM, resulting in joint pain, stiffness, and reduced mobility.

SOX9 (SRY-related HMG-box gene 9) is a transcription factor that belongs to the SOX family of proteins, which are characterized by a high mobility group (HMG) box DNA-binding domain. SOX9 plays crucial roles in various developmental processes, including sex determination, chondrogenesis, and neurogenesis.

As a transcription factor, SOX9 binds to specific DNA sequences in the promoter or enhancer regions of its target genes and regulates their expression. In the context of sex determination, SOX9 is essential for the development of Sertoli cells in the male gonad, which are responsible for supporting sperm production. SOX9 also plays a role in maintaining the undifferentiated state of stem cells and promoting cell differentiation in various tissues.

Mutations in the SOX9 gene have been associated with several human genetic disorders, including campomelic dysplasia, a severe skeletal disorder characterized by bowed legs, and sex reversal in individuals with XY chromosomes.

Immunohistochemistry (IHC) is a technique used in pathology and laboratory medicine to identify specific proteins or antigens in tissue sections. It combines the principles of immunology and histology to detect the presence and location of these target molecules within cells and tissues. This technique utilizes antibodies that are specific to the protein or antigen of interest, which are then tagged with a detection system such as a chromogen or fluorophore. The stained tissue sections can be examined under a microscope, allowing for the visualization and analysis of the distribution and expression patterns of the target molecule in the context of the tissue architecture. Immunohistochemistry is widely used in diagnostic pathology to help identify various diseases, including cancer, infectious diseases, and immune-mediated disorders.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

The skull base is the lower part of the skull that forms the floor of the cranial cavity and the roof of the facial skeleton. It is a complex anatomical region composed of several bones, including the frontal, sphenoid, temporal, occipital, and ethmoid bones. The skull base supports the brain and contains openings for blood vessels and nerves that travel between the brain and the face or neck. The skull base can be divided into three regions: the anterior cranial fossa, middle cranial fossa, and posterior cranial fossa, which house different parts of the brain.

Microdissection is a surgical technique that involves the use of a microscope to allow for precise, minimalistic dissection of tissue. It is often used in research and clinical settings to isolate specific cells, tissues or structures while minimizing damage to surrounding areas. This technique can be performed using various methods such as laser capture microdissection (LCM) or manual microdissection with microsurgical tools. The size and scale of the dissection required will determine the specific method used. In general, microdissection allows for the examination and analysis of very small and delicate structures that would otherwise be difficult to access and study.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

24,25-Dihydroxyvitamin D3 is a metabolite of vitamin D3, also known as calcitriol. It is formed in the body through the hydroxylation of vitamin D3 by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase, which is primarily found in the kidneys.

24,25-Dihydroxyvitamin D3 plays a role in regulating calcium and phosphate metabolism, but its functions are not as well understood as those of other vitamin D metabolites. Some studies have suggested that it may have anti-inflammatory effects and may be involved in the regulation of cell growth and differentiation. However, more research is needed to fully understand the physiological role of this compound.

It's important to note that 24,25-Dihydroxyvitamin D3 is not typically used as a therapeutic agent, and its levels in the body are not routinely measured in clinical practice.

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