Abstract:

Endochondral ossification is a complex and ordered biological process that is precisely regulated by many force-sensitive factors. However, biomechanical agents affect the expression of these factors. The expression of Indian hedgehog(IHH) improved after mechanical force stimulation was applied to the chondrocyte, and cell proliferation was promoted. IHH coordinates the proliferation, maturation, and differentiation of the chondrocyteby forming a negative feedback loop with parathyroid hormone related protein(PTHrP). Moreover, IHH is necessary for chondrocyte proliferation and differentiation in a pathway that cannot be dependent on PTHrP. Core binding factor-α1 plays an important role not only in the chondrogenesis but also in the process of vascular invasion, thereby inducing vascular invasion and endochondral ossification by stimulating the expression of vascular endothelial growth factor(VEGF) in hypertrophic chondrocytes. VEGFA improves the permeability of blood vessels by stimulating the proliferation and migration of endothelial cells. Meanwhile, the matrix degradation of hypertrophic chondrocytes and blood vessels is key to endochondral ossification. VEGF coordinates the relationship of chondrocyte proliferation, osteoclast function, extracellular matrix rebuilding, vascular proliferation, and bone formation. Biomechanical agents affect the expression of force-sensitive factors and the progress of endochondral ossification. Understanding the molecular mechanism underlying the abovementioned phenomenon will benefit our research onbone formation and repair.

Key words: endochondral ossification, mechanical stress, Indian hedgehog, core binding factor-α1, vascular endothelial growth factor