Shang Jin, Liu Huan, Li Jie, Zhou Yue
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, No. 183 Xinqiao Main Street, Shapingba District, Chongqing, People's Republic of China.
Curr Stem Cell Res Ther. 2014 Mar;9(2):141-7. doi: 10.2174/1574888x09666131230142459.
Articular cartilage is an avascular tissue without innervations, characterized by low cell density and abundant extracellular matrix (ECM). These characteristics leave articular cartilage with very limited capacity of repair and regeneration. Common injuries and degenerative diseases often lead to progressive dysfunction of articular cartilage, even joint arthroplasty finally. In recent years, cell-based therapies targeting cartilage-related diseases have aroused strong interests of doctors and researchers. Mesenchymal stem cells (MSCs) have the ability to self-renew and differentiate into multilineage cell types such as osteocytes, chondrocytes and adipocytes. The chondrogenic differentiation of MSCs is regulated by many factors, including oxygen tensions. Evidences have suggested that low oxygen tension or hypoxia is involved in the chondrogenic differentiation of MSCs. Expansion and chondrogenic induction of MSCs under hypoxia generally result in enhanced chondrogenic differentiation, although with some inconsistent result. Hypoxia inducible factors (HIFs) are a group of transcription factors. Their stability and transactivation may be essential to the effect of hypoxia on the chondrogenic differentiation of MSCs. PI3K/Akt/FoxO pathways may also be involved in enhanced chondrogenic differentiation under hypoxia. In this review, we discuss the roles of hypoxic conditions in chondrogenic differentiation of MSCs and mechanisms underlying cellular responses to hypoxia.
关节软骨是一种无血管、无神经支配的组织，其特点是细胞密度低且细胞外基质（ECM）丰富。这些特性使得关节软骨的修复和再生能力非常有限。常见的损伤和退行性疾病常常导致关节软骨进行性功能障碍，最终甚至需要进行关节置换术。近年来，针对软骨相关疾病的细胞疗法引起了医生和研究人员的浓厚兴趣。间充质干细胞（MSCs）具有自我更新能力，并能分化为多种细胞类型，如骨细胞、软骨细胞和脂肪细胞。MSCs的软骨形成分化受多种因素调节，包括氧张力。有证据表明，低氧张力或缺氧参与了MSCs的软骨形成分化。在缺氧条件下对MSCs进行扩增和软骨形成诱导通常会导致软骨形成分化增强，尽管结果存在一些不一致。缺氧诱导因子（HIFs）是一组转录因子。它们的稳定性和反式激活作用可能对缺氧影响MSCs软骨形成分化的效应至关重要。PI3K/Akt/FoxO信号通路也可能参与缺氧条件下增强的软骨形成分化过程。在本综述中，我们讨论了缺氧条件在MSCs软骨形成分化中的作用以及细胞对缺氧反应的潜在机制。
