Target type: biologicalprocess
The process whose specific outcome is the progression of the cartilage that will provide a scaffold for mineralization of endochondral bones. [GOC:dph]
Endochondral bone morphogenesis is a complex process that involves the formation of bone from a cartilaginous template. This process is essential for the development of most bones in the body, and it can be divided into several distinct stages:
**1. Mesenchymal Condensation and Chondrogenesis:**
- Mesenchymal cells, derived from the mesoderm, condense and differentiate into chondroblasts.
- These chondroblasts secrete a specialized extracellular matrix rich in collagen type II, proteoglycans (mainly aggrecan), and other components.
- The accumulating matrix surrounds the chondroblasts, creating a cartilaginous model of the future bone.
**2. Cartilage Growth and Differentiation:**
- The cartilaginous model undergoes significant growth through interstitial growth (division of chondrocytes within the matrix) and appositional growth (addition of new chondrocytes at the periphery).
- Chondrocytes within the developing cartilage differentiate into distinct zones:
- **Zone of resting cartilage:** Chondrocytes are quiescent and exhibit low metabolic activity.
- **Zone of proliferating cartilage:** Chondrocytes undergo rapid division, increasing the length of the cartilage model.
- **Zone of hypertrophic cartilage:** Chondrocytes enlarge significantly, accumulating glycogen and other macromolecules.
- **Zone of calcified cartilage:** The hypertrophic chondrocytes secrete alkaline phosphatase, which initiates calcification of the cartilage matrix.
**3. Vascular Invasion and Osteoblast Differentiation:**
- Blood vessels invade the calcified cartilage, bringing in osteoprogenitor cells and nutrients.
- These osteoprogenitor cells differentiate into osteoblasts, which deposit bone matrix onto the calcified cartilage template.
**4. Bone Formation and Remodeling:**
- Osteoblasts lay down bone matrix, forming trabeculae (spongy bone) within the cartilage model.
- As the bone formation progresses, the cartilage is gradually replaced by bone.
- The process of bone remodeling, involving bone resorption by osteoclasts and bone deposition by osteoblasts, continues throughout life, maintaining bone homeostasis and adapting to mechanical demands.
**5. Formation of the Growth Plate:**
- At the ends of long bones, a specialized region known as the growth plate remains cartilaginous.
- The growth plate is responsible for longitudinal bone growth throughout childhood and adolescence.
- As the individual reaches skeletal maturity, the growth plate closes, marking the end of bone growth.
**Key Regulators and Signaling Pathways Involved in Endochondral Bone Morphogenesis:**
- **Growth factors:** Bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), Indian hedgehog (Ihh), and parathyroid hormone-related protein (PTHrP) play crucial roles in chondrocyte proliferation, differentiation, and matrix deposition.
- **Transcription factors:** Sox9, Runx2, and Sclerostin regulate gene expression and control chondrocyte differentiation and osteoblast activity.
- **Signaling pathways:** Wnt, TGF-β, and Notch pathways are involved in cell fate decisions, growth, and differentiation during bone formation.
Endochondral bone morphogenesis is a complex and tightly regulated process. Dysregulation of any of the involved factors or signaling pathways can lead to skeletal disorders.'
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Protein | Definition | Taxonomy |
---|---|---|
Transient receptor potential cation channel subfamily V member 4 | A transient receptor potential cation channel TRPV4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:Q9HBA0] | Homo sapiens (human) |
Cystathionine beta-synthase | A cystathionine beta-synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35520] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
aminooxyacetic acid | (aminooxy)acetic acid : A member of the class of hydroxylamines that is acetic acid substituted at postion 2 by an aminooxy group. It is a compound which inhibits aminobutyrate aminotransferase activity in vivo, resulting in increased levels of gamma-aminobutyric acid in tissues. Aminooxyacetic Acid: A compound that inhibits aminobutyrate aminotransferase activity in vivo, thereby raising the level of gamma-aminobutyric acid in tissues. | amino acid; hydroxylamines; monocarboxylic acid | anticonvulsant; EC 2.6.1.19 (4-aminobutyrate--2-oxoglutarate transaminase) inhibitor; EC 4.2.1.22 (cystathionine beta-synthase) inhibitor; nootropic agent |
aurintricarboxylic acid | aurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'. Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues. | monohydroxybenzoic acid; quinomethanes; tricarboxylic acid | fluorochrome; histological dye; insulin-like growth factor receptor 1 antagonist |
cannabinol | Cannabinol: A physiologically inactive constituent of Cannabis sativa L. | dibenzopyran | |
hypericin | |||
cannabichromene | 1-benzopyran | ||
(6ar-trans)-isomer of tetrahydrocannabivarin 9 | |||
hc 030031 | 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide: a TRPA1 channel blocker | ||
hc-067047 | HC-067047: a TRPA1 antagonist; structure in first source | ||
rn 1734 | RN 1734: a TRPV4 antagonist; structure in first source | ||
agathisflavone | agathisflavone : A biflavonoid that is obtained by oxidative coupling of two molecules of apigenin resulting in a bond between positions C-6 and C-8 of the two chromene rings. agathisflavone: bis-apigenin coupled at 6 and 8 positions; isolated from the plant Canarium manii; has hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity | biaryl; biflavonoid; hydroxyflavone | antineoplastic agent; antiviral agent; hepatoprotective agent; metabolite |
cupressuflavone | cupressuflavone : A biflavonoid that is obtained by oxidative coupling of two molecules of apigenin resulting in a bond between positions C-8 of the two chromene rings respectively. Isolated from Cupressus sempervirens and Juniperus occidentalis, it exhibits free radical scavenging and antielastase activities. cupressuflavone: from Cupressus macrocarpa; structure in first source | biflavonoid; hydroxyflavone; ring assembly | EC 3.4.21.37 (leukocyte elastase) inhibitor; metabolite; radical scavenger |
myricetin | 7-hydroxyflavonol; hexahydroxyflavone | antineoplastic agent; antioxidant; cyclooxygenase 1 inhibitor; food component; geroprotector; hypoglycemic agent; plant metabolite | |
cannabigerol | cannabigerol : A member of the class of resorcinols that is resorcinol which is substituted by a (2E)-3,7-dimethylocta-2,6-dien-1-yl group at position 2 and by a pentyl group at position 5. It is a natural product found in Cannabis sativa and Helichrysum species. cannabigerol: RN given refers to (E)-isomer; structure given in first source | phytocannabinoid; resorcinols | anti-inflammatory agent; antibacterial agent; antioxidant; appetite enhancer; cannabinoid receptor agonist; neuroprotective agent; plant metabolite |
podocarpusflavone a | podocarpusflavone A: isolated from Podocarpus imbricatus | flavonoid oligomer | |
rubrolide a | rubrolide A: from Synoicum prunum; structure in first source | ||
cannabidivarin | cannabidivarin: from Cannabis sativa | monoterpenoid | |
gsk 1016790a | GSK1016790A : A tertiary carboxamide that is piperazine in which one of the amino groups has undergone condensation with the carboxy group of N-[(2,4-dichlorophenyl)sulfonyl]-L-serine, while the other has undergone condensation with the carboxy group of N-(1-benzothiophen-2-ylcarbonyl)-L-leucine. It is a cell-permeable, potent and selective agonist of the TRPV4 (transient receptor potential vanilloid 4) channel. | 1-benzothiophenes; aromatic primary alcohol; dichlorobenzene; N-acylpiperazine; sulfonamide; tertiary carboxamide | TRPV4 agonist |