低氧对间充质干细胞迁移及成骨分化的影响

间充质干细胞(MSCs)由于具有来源广泛、自我更新及多向分化能力,是骨组织工程上的重要种子细胞.MSCs在体内的生理环境及植入后都是一个低氧状态,低氧是影响MSCs迁移、成骨分化的一个重要因素.大部分研究认为低氧通过调控相关趋化因子及细胞因子等促进MSCs向低氧处迁移,涉及的相关因子包括整合素家族、基质金属蛋白酶、Rho-GTPase家族、SDF-1α/CXCR4信号、OPN/CD44信号等.低氧诱导因子-1α(HIF-1α)信号可促进骨形成、骨修复,然而,低氧对MSCs成骨分化的影响尚存在较大争议,低氧环境下BMP-Smads、WNT/β-catenin、Notch、Hedgehog等成骨相关通路的变化是影响MSCs成骨分化的因素之一.本文就低氧对MSCs迁移及成骨分化的影响及机制做一综述.

Effects of hypoxia on migration and osteogenic differentiation of mesenchymal stem cells

Due to the extensive sources, self-renewal and ability of multi-directional differentiation, mesenchy-mal stem cells (MSCs) are essential seed cells for bone tissue engineering. The environment after transplantation and physiological environment in vivo where MSCs live are a hypoxic state. Hypoxia is an important factor affecting MSCs migration and osteogenic differentiation. Most research suggests that hypoxia promotes the migration of MSCs by regu-lating the related chemotactic factors and cytokines. The relevant factors include integrin family, matrix metalloproteinas-es, Rho-GTPase family, SDF-1α/CXCR4 signal, OPN/CD44 signal. However, the effect of hypoxia on the osteogenic differentiation of MSCs remains controversial. The variations of signaling pathways of BMP-Smads, WNT/β-catenin, Notch, Hedgehog in hypoxia may be one of the factors that influence the osteogenic differentiation of MSCs. In this pa-per, the effects of hypoxia on the migration and osteogenic differentiation of MSCs and its mechanism will be discussed.