Abstract
Endochondral ossification (EO), by which long bones of the axial skeleton form, is a tightly regulated process involving chondrocyte maturation with successive stages of proliferation, maturation, and hypertrophy, accompanied by cartilage matrix synthesis, calcification, and angiogenesis, followed by osteoblast-mediated ossification. This developmental sequence reappears during fracture repair and in osteoarthritic etiopathology. These similarities suggest that EO, and the cells involved, are of great clinical importance for bone regeneration as it could provide novel targeted approaches to increase specific signaling to promote fracture healing, and if regulated appropriately in the treatment of osteoarthritis. The long-held accepted dogma states that hypertrophic chondrocytes are terminally differentiated and will eventually undergo apoptosis. In this mini review, we will explore recent evidence from experiments that revisit the idea that hypertrophic chondrocytes have pluripotent capacity and may instead transdifferentiate into a specific sub-population of osteoblast cells. There are multiple lines of evidence, including our own, showing that local, selective alterations in cartilage extracellular matrix (ECM) remodeling also indelibly alter bone quality. This would be consistent with the hypothesis that osteoblast behavior in long bones is regulated by a combination of their lineage origins and the epigenetic effects of chondrocyte-derived ECM which they encounter during their recruitment. Further exploration of these processes could help to unlock potential novel targets for bone repair and regeneration and in the treatment of osteoarthritis.
Highlights
The mobility provided by a robust locomotor skeletal system is a major determinant of human health and quality of life
We will (i) explore recent evidence that revisits the idea that hypertrophic chondrocytes may transdifferentiate into a specific sub-population of osteoblast cells and (ii) share data suggesting that osteoblast behavior in this sub-population relies partly upon a direct contribution from the cartilage extracellular matrix (ECM) composition
There are multiple lines of evidence, including our own, showing that local, selective alterations in cartilage ECM remodeling indelibly alter bone quality. This would be consistent with the hypothesis that osteoblast behavior in long bones is regulated by a combination of their lineage origins and the epigenetic effects of chondrocyte-derived ECM which they encounter during their recruitment (Figure 2)
Summary
The mobility provided by a robust locomotor skeletal system is a major determinant of human health and quality of life. Endochondral ossification is initiated by migration of mesenchymal cells to form pre-cartilage condensations, which undergo differentiation into chondrocytes that secrete ECM rich in aggrecan (Acan) and collagen type II.
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