State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing 100191, People's Republic of China.
Biomed Mater. 2021 Feb 18;16(2):022006. doi: 10.1088/1748-605X/abdb73.
The repair and treatment of articular cartilage injury is a huge challenge of orthopedics. Currently, most of the clinical methods applied in treating cartilage injuries are mainly to relieve pains rather than to cure them, while the strategy of tissue engineering is highly expected to achieve the successful repair of osteochondral defects. Clear understandings of the physiological structures and mechanical properties of cartilage, bone and osteochondral tissues have been established, but the understanding of their physiological heterogeneity still needs further investigation. Apart from the gradients in the micromorphology and composition of cartilage-to-bone extracellular matrixes, an oxygen gradient also exists in natural osteochondral tissue. The response of hypoxia-inducible factor (HIF)-mediated cells to oxygen would affect the differentiation of stem cells and the maturation of osteochondral tissue. This article reviews the roles of oxygen level and HIF signaling pathway in the development of articular cartilage tissue, and their prospective applications in bone and cartilage tissue engineering. The strategies for regulating HIF signaling pathway and how these strategies finding their potential applications in the regeneration of integrated osteochondral tissue are also discussed.
关节软骨损伤的修复和治疗是骨科的一大挑战。目前，临床上应用于治疗软骨损伤的大多数方法主要是缓解疼痛，而不是治愈，而组织工程学策略则有望成功修复骨软骨缺损。人们已经对软骨、骨和骨软骨组织的生理结构和力学性能有了清晰的认识，但对其生理异质性的认识仍需进一步研究。除了软骨到骨细胞外基质的微观形态和成分的梯度外，天然骨软骨组织中还存在氧梯度。缺氧诱导因子 (HIF) 介导的细胞对氧的反应会影响干细胞的分化和骨软骨组织的成熟。本文综述了氧水平和 HIF 信号通路在关节软骨组织发育中的作用及其在骨和软骨组织工程中的潜在应用。还讨论了调节 HIF 信号通路的策略，以及这些策略如何在整合的骨软骨组织再生中找到潜在的应用。
