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论文摘要

力敏感因子对软骨内成骨的调控作用

The function of force-sensitive factors in endochondral ossification

作者:王亚斐,刘畅

Author:Wang Yafei, Liu Chang

收稿日期:2014-08-02          年卷(期)页码:2015,42(5):615-619

期刊名称:国际口腔医学杂志

Journal Name:International Journal of Stomatology

关键字:软骨内成骨,生物力,印第安刺猬蛋白,核心结合因子-α1,血管内皮细胞生长因子,

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

基金项目:

吉林省卫生厅科研基金(2008Z010);吉林大学基本科研 业务费-科学前沿与交叉学科创新项目(200903225)

中文摘要

软骨内成骨是一个复杂有序的生物学过程,依赖于一系列力敏感因子的精确调控,而生物力影响着软骨内成骨中力敏感因子的表达。对软骨细胞施加力学刺激后,印第安刺猬蛋白(IHH)表达增加,细胞增殖加快。IHH通过与甲状旁腺素-甲状旁腺素相关肽(PTHrP)受体形成的负反馈环路协调软骨细胞的增殖、成熟与分化,而IHH在调控软骨细胞增殖分化方面并非是PTHrP依赖性的。核心结合因子-α1不仅在软骨形成中,亦在血管侵入软骨过程中发挥作用,可刺激肥大软骨细胞中的血管内皮生长因子(VEGF)诱导血管侵入,促进软骨内骨化。VEGFA通过刺激内皮细胞的增殖和迁徙增加血管的通透性,而肥大软骨细胞基质降解、血管侵入是软骨内成骨的关键。VEGF在软骨内成骨过程中协调着软骨细胞增殖、破骨细胞功能、细胞外基质改建、血管增生和骨形成间的关系。生物力影响着软骨内成骨力敏感因子的表达,进而影响着软骨内成骨进程,理解其中的分子机制将有利于骨形成和骨修复研究。

英文摘要

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.

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