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.

中文翻译：

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焦亡：退行性骨和关节疾病中细胞之间和平共存的破坏者


随着人们年龄的增长，退行性骨和关节疾病（DBJD）变得更加普遍。当中老年人被诊断患有骨质疏松症（OP）、骨关节炎（OA）和椎间盘退变（IVDD）等一种或多种疾病时，通常预示着长期疼痛和功能下降的发生。慢性炎症已被确定为各种退行性疾病（包括 DBJD）的根本原因。最近，细胞焦亡（一种由炎症小体介导的程序性细胞死亡（PCD）形式）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 DBJD 的潜在靶点。本综述探讨了焦亡途径在骨和关节发育中的生理和病理作用及其与 DBJD 的关系。同时，详细阐述了骨髓和关节中单个细胞类型焦亡的分子机制，以及 DBJD 背景下不同细胞类型之间的相互作用。此外，本综述提出了最新的令人信服的证据，支持调节 DBJD 治疗焦亡途径的想法，并讨论了涉及焦亡调节的各种治疗策略的潜力、局限性和挑战。总之，这篇综述提出了 DBJD 背景下不受调控的细胞焦亡途径的一个有趣的身份，这是对退化环境中细胞之间和平共存的破坏。 在 DBJD 的延长过程中，焦亡途径通过不同细胞类型中焦亡级联之间的串扰来维持其活性，从而加剧整个骨髓和关节退化环境的炎症环境。相应地，细胞焦亡调节疗法成为 DBJD 临床治疗的一个有前景的选择。