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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