School of Rehabilitation and Health Preservation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry, Tokyo 142-8555, Japan.
Ageing Res Rev. 2022 May;77:101608. doi: 10.1016/j.arr.2022.101608. Epub 2022 Mar 11.
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.
成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方面起着关键作用。大量证据表明，成骨细胞及其腔室在衰老骨骼中表现出形态变化，表明成骨细胞在骨衰老中起潜在作用。值得注意的是，最近的研究揭示了衰老的成骨细胞具有机械敏感性受损、细胞衰老积累、功能失调的陷窝/管腔重塑以及退化的陷窝-管腔网络等特征。然而，成骨细胞的详细分子机制尚不清楚。尽管如此，通过先进的 RNA 测序 (RNA-seq) 技术分析的成骨细胞转录组已确定了几个与骨衰老相关的基因和信号通路，如 Wnt、Bmp/TGF 和 Jak-STAT。此外，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恶化中的成骨细胞。在这篇综述中，我们总结了衰老骨骼和成骨细胞的特征，并讨论了成骨细胞在与年龄相关的骨丢失和骨质量受损中的机制。此外，我们还提供了在研究成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 可以解码衰老成骨细胞中的转录组信息；因此，一旦开发出针对成骨细胞的成熟标准化方案，这项技术就可以促进基于成骨细胞的新型单细胞研究。有趣的是，对成骨细胞机制的深入了解有助于确定与年龄相关的骨质疏松症和脆弱性骨折的有前途的靶点和有效治疗方法。
