Damage to osteochondral (OC) tissues can lead to pain, loss of motility, and progress to osteoarthritis. Tissue engineering approaches offer the possibility of replacing damaged tissues and restoring joint function; however, replicating the spatial and functional heterogeneity of native OC tissue remains a pressing challenge. Chondrocytes in healthy cartilage exist in relatively low-oxygen conditions, while osteoblasts in the underlying bone experience higher oxygen pressures. Such oxygen gradients also exist in the limb bud, where they influence OC tissue development. The cellular response to these spatial variations in oxygen pressure, which is mediated by the hypoxia inducible factor (HIF) pathway, plays a central role in regulating osteo- and chondrogenesis by directing progenitor cell differentiation and promoting and maintaining appropriate extracellular matrix production. Understanding the role of the HIF pathway in OC tissue development may enable new approaches to engineer OC tissue. In this review, we discuss strategies to spatially and temporarily regulate the HIF pathway in progenitor cells to create functional OC tissue for regenerative therapies.

中文翻译：

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骨软骨组织工程中的缺氧诱导因子-1α。

对骨软骨（OC）组织的损害可导致疼痛，运动能力丧失并发展为骨关节炎。组织工程学方法提供了替换受损组织和恢复关节功能的可能性。然而，复制天然OC组织的空间和功能异质性仍然是一个紧迫的挑战。健康软骨中的软骨细胞存在于相对较低的氧气条件下，而下方骨骼中的成骨细胞则承受较高的氧气压力。这种氧梯度也存在于肢芽中，在那里它们会影响OC组织的发育。细胞对氧气压力的这些空间变化的反应，这是由缺氧诱导因子（HIF）途径介导的，通过指导祖细胞分化并促进和维持适当的细胞外基质产生，在调节骨和软骨形成中起着重要作用。了解HIF途径在OC组织发育中的作用可能会为工程OC组织提供新的方法。在这篇综述中，我们讨论了在空间和临时调节祖细胞中HIF途径以创建功能性OC组织进行再生疗法的策略。