Page last updated: 2024-10-24

cartilage development involved in endochondral bone morphogenesis

Definition

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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Proteins (2)

ProteinDefinitionTaxonomy
Transient receptor potential cation channel subfamily V member 4A transient receptor potential cation channel TRPV4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:Q9HBA0]Homo sapiens (human)
Cystathionine beta-synthaseA cystathionine beta-synthase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P35520]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
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 acidaurintricarboxylic 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
cannabinolCannabinol: A physiologically inactive constituent of Cannabis sativa L.dibenzopyran
hypericin
cannabichromene1-benzopyran
(6ar-trans)-isomer of tetrahydrocannabivarin 9
hc 0300312-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide: a TRPA1 channel blocker
hc-067047HC-067047: a TRPA1 antagonist; structure in first source
rn 1734RN 1734: a TRPV4 antagonist; structure in first source
agathisflavoneagathisflavone : 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
cupressuflavonecupressuflavone : 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
myricetin7-hydroxyflavonol;
hexahydroxyflavone
antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite
cannabigerolcannabigerol : 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 apodocarpusflavone A: isolated from Podocarpus imbricatusflavonoid oligomer
rubrolide arubrolide A: from Synoicum prunum; structure in first source
cannabidivarincannabidivarin: from Cannabis sativamonoterpenoid
gsk 1016790aGSK1016790A : 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