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Course: MCAT > Unit 2

Lesson 3: Foundation 3: Organ Systems

Skeletal system: Bone development


Ossification begins as early as the second month of embryonic development and can continue into early adulthood. The process relies on properly functioning osteochondroprogenitor cells, which are mesenchymal stem cells that can differentiate into chondrocytes or osteoblasts. In these cells, expression of the transcription factors CBFA1/RUNX2 and OSX induces osteoblast differentiation, and expression of the transcription factors SOX9, L-SOX5, and SOX6 induces chondrocyte differentiation.
Depending on the type of bone, ossification occurs through one of two processes:
During endochondral ossification, bone tissue systematically replaces hyaline cartilage, resulting in the formation of long bones. The process begins when mesoderm-derived mesenchymal cells differentiate into chondrocytes, which proliferate and secrete extracellular matrix (ECM), forming a cartilage model resembling the shape of future bone. Chondrocytes near the center then undergo hypertrophy, adding collagen and fibronectin to their ECM. Calcification of the ECM prevents nutrients from reaching the chondrocytes, causing them to undergo apoptosis. The resulting cell death creates voids and allows blood vessels to invade and further enlarge the spaces, bringing osteogenic cells and triggering the transformation of the perichondrium to periosteum. Osteoblasts from the periosteum create a thickened region of compact bone called a bone collar, around which the primary ossification center forms. While bone is replacing cartilage around the primary ossification center, cartilage continues to proliferate at the ends of the bone. These proliferative areas become the epiphyseal plates, or bone plates, which will not close until adolescence. After birth, the process repeats itself in the secondary ossification centers. A schematic of this process is shown in Figure 1.
Figure 1 Steps of endochondral ossification: formation of a bone collar of compact bone around hyaline cartilage (A), cavitation of cartilage (B), invasion by periosteal bud and spongy bone formation (C), formation of medullary cavity as ossification continues (D), ossification of the epiphyses (E).
During intramembranous ossification, mesenchymal progenitor cells differentiate directly into osteoblasts, followed by the development of flat bones. The steps of intramembranous ossification are shown in Figure 2.
Figure 2 Steps of intramembranous ossification: ossification center appears in fibrous connective tissue membrane (A), bone matrix is secreted (B), woven bone and periosteum form (C), bone collar of compact bone forms and marrow appears (D).
Passage info adapted from Breeland G, Sinkler MA, Menezes RG. Embryology, Bone Ossification. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Schematics adapted from https://www.tobig.eu/bone-101/bone-101/bone-formation-and-remodeling/
What is the make-up of the protein secreted by chondrocytes that is an important structural component of both cartilage and bone?
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