骨老化中的骨细胞：进展、挑战和未来展望,Ageing Research Reviews

骨细胞在维持骨稳态和调节骨骼对激素和机械负荷的反应中起关键作用。大量证据表明，骨细胞及其腔隙在老化骨中表现出形态变化，表明骨细胞在骨老化中的潜在参与。值得注意的是，最近的研究已经破译了老化的骨细胞具有诸如机械敏感性受损、细胞累积衰老、功能失调的腔隙周围/小管重塑和退化的腔隙-小管网络等特征。然而，骨细胞的详细分子机制仍不清楚。尽管如此，通过高级 RNA 测序 (RNA-seq) 技术分析的骨细胞转录组已经确定了几种与骨老化相关的基因和信号通路，例如 Wnt、Bmp/TGF 和 Jak-STAT。而且，炎症、免疫功能障碍、能量短缺和激素反应受损可能会影响与年龄相关的骨退化中的骨细胞。在这篇综述中，我们总结了老化骨和骨细胞的特征，并讨论了与年龄相关的骨丢失和骨质量受损的骨细胞机制。此外，我们提供了对研究骨细胞转录组时面临的挑战及其可能的解决方案的见解。我们还强调单细胞 RNA-seq 可以解码衰老骨细胞中的转录组信息。因此，一旦开发了专门针对骨细胞的完善的标准化协议，该技术就可以促进新的基于单细胞的骨细胞研究。有趣的是，

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Osteocytes play a critical role in maintaining bone homeostasis and in regulating skeletal response to hormones and mechanical loading. Substantial evidence have demonstrated that osteocytes and their lacunae exhibit morphological changes in aged bone, indicating the underlying involvement of osteocytes in bone aging. Notably, recent studies have deciphered aged osteocytes to have characteristics such as impaired mechanosensitivity, accumulated cellular senescence, dysfunctional perilacunar/canalicular remodeling, and degenerated lacuna-canalicular network. However, detailed molecular mechanisms of osteocytes remain unclear. Nonetheless, osteocyte transcriptomes analyzed via advanced RNA sequencing (RNA-seq) techniques have identified several bone aging-related genes and signaling pathways, such as Wnt, Bmp/TGF, and Jak-STAT. Moreover, inflammation, immune dysfunction, energy shortage, and impaired hormone responses possibly affect osteocytes in age-related bone deterioration. In this review, we summarize the hallmarks of aging bone and osteocytes and discuss osteocytic mechanisms in age-related bone loss and impaired bone quality. Furthermore, we provide insights into the challenges faced and their possible solutions when investigating osteocyte transcriptomes. We also highlight that single-cell RNA-seq can decode transcriptomic messages in aged osteocytes; therefore, this technique can promote novel single cell-based investigations in osteocytes once a well-established standardized protocol specific for osteocytes is developed. Interestingly, improved understanding of osteocytic mechanisms have helped identify promising targets and effective therapies for aging-related osteoporosis and fragile fractures.