Li Zhichao, Cheng Wenxiang, Gao Kuanhui, Liang Songlin, Ke Liqing, Wang Mengjie, Fan Jilin, Li Dandan, Zhang Peng, Xu Zhanwang, Li Nianhu
First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, China; Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China; Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
J Adv Res. 2025 May;71:227-262. doi: 10.1016/j.jare.2024.06.010. Epub 2024 Jun 13.
As people age, degenerative bone and joint diseases (DBJDs) become more prevalent. When middle-aged and elderly people are diagnosed with one or more disorders such as osteoporosis (OP), osteoarthritis (OA), and intervertebral disc degeneration (IVDD), it often signals the onset of prolonged pain and reduced functionality. Chronic inflammation has been identified as the underlying cause of various degenerative diseases, including DBJDs. Recently, excessive activation of pyroptosis, a form of programed cell death (PCD) mediated by inflammasomes, has emerged as a primary driver of harmful chronic inflammation. Consequently, pyroptosis has become a potential target for preventing and treating DBJDs.
This review explored the physiological and pathological roles of the pyroptosis pathway in bone and joint development and its relation to DBJDs. Meanwhile, it elaborated the molecular mechanisms of pyroptosis within individual cell types in the bone marrow and joints, as well as the interplay among different cell types in the context of DBJDs. Furthermore, this review presented the latest compelling evidence supporting the idea of regulating the pyroptosis pathway for DBJDs treatment, and discussed the potential, limitations, and challenges of various therapeutic strategies involving pyroptosis regulation.
In summary, an interesting identity for the unregulated pyroptosis pathway in the context of DBJDs was proposed in this review, which was undertaken as a spoiler of peaceful coexistence between cells in a degenerative environment. Over the extended course of DBJDs, pyroptosis pathway perpetuated its activity through crosstalk among pyroptosis cascades in different cell types, thus exacerbating the inflammatory environment throughout the entire bone marrow and joint degeneration environment. Correspondingly, pyroptosis regulation therapy emerged as a promising option for clinical treatment of DBJDs.
随着人们年龄的增长，退行性骨与关节疾病（DBJDs）变得愈发普遍。当中老年人被诊断出患有一种或多种疾病，如骨质疏松症（OP）、骨关节炎（OA）和椎间盘退变（IVDD）时，往往预示着长期疼痛和功能减退的开始。慢性炎症已被确认为包括DBJDs在内的各种退行性疾病的根本原因。最近，由炎性小体介导的一种程序性细胞死亡（PCD）形式——细胞焦亡的过度激活，已成为有害慢性炎症的主要驱动因素。因此，细胞焦亡已成为预防和治疗DBJDs的潜在靶点。
本综述探讨了细胞焦亡途径在骨骼和关节发育中的生理和病理作用及其与DBJDs的关系。同时，阐述了骨髓和关节中单个细胞类型内细胞焦亡的分子机制，以及在DBJDs背景下不同细胞类型之间的相互作用。此外，本综述还提供了支持调节细胞焦亡途径用于治疗DBJDs这一观点的最新有力证据，并讨论了涉及细胞焦亡调节的各种治疗策略的潜力、局限性和挑战。
总之，本综述提出了在DBJDs背景下不受调控的细胞焦亡途径的一个有趣特征，即在退行性环境中它是细胞和平共处的破坏者。在DBJDs的漫长病程中，细胞焦亡途径通过不同细胞类型中细胞焦亡级联反应之间的相互作用持续其活性，从而加剧整个骨髓和关节退变环境中的炎症环境。相应地，细胞焦亡调节疗法成为DBJDs临床治疗的一个有前景的选择。
