低氧对间充质干细胞迁移及成骨分化的影响

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

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。

Due to the extensive sources, self-renewal and ability of multi-directional differentiation, mesenchymal 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 regulating the related chemotactic factors and cytokines. The relevant factors include integrin family, matrix metalloproteinases, 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 paper, the effects of hypoxia on the migration and osteogenic differentiation of MSCs and its mechanism will be discussed.