Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Ageing Res Rev. 2023 Sep;90:102024. doi: 10.1016/j.arr.2023.102024. Epub 2023 Jul 31.
As the most common bone disease, osteoporosis (OP) increases bone fragility and makes patients more vulnerable to the threat of osteoporotic fractures. With the ageing population in today's society, OP has become a huge and growing public health problem. Unfortunately, the clear pathogenesis of OP is still under exploration, and effective interventions are still scarce. Therefore, exploring new targets for pharmacological interventions to develop promising therapeutic drugs for OP is of great clinical value. Previous studies have shown that normal bone remodeling depends on proteostasis, whereas loss of proteostasis during ageing leads to the dysfunctional proteostasis network (PN) that fails to maintain bone homeostasis. Nevertheless, only a few studies have revealed the pathophysiological relationship between bone metabolism and a single component of PN, yet the role of PN as a whole in the pathogenesis of OP is still under investigation. This review comprehensively summarized the role of PN in the pathogenesis of OP and further discussed the potential of PN as innovative drug targets for the therapy of OP.
作为最常见的骨骼疾病,骨质疏松症(OP)会增加骨骼脆弱性,使患者更容易受到骨质疏松性骨折的威胁。随着当今社会人口老龄化,OP 已成为一个巨大且日益严重的公共卫生问题。不幸的是,OP 的明确发病机制仍在探索中,有效的干预措施仍然匮乏。因此,探索新的药物干预靶点,开发治疗 OP 的有前途的治疗药物具有重要的临床价值。先前的研究表明,正常的骨骼重塑依赖于蛋白质稳态,而衰老过程中蛋白质稳态的丧失会导致功能失调的蛋白质稳态网络(PN)无法维持骨骼内稳态。然而,只有少数研究揭示了骨代谢与 PN 单个成分之间的病理生理学关系,而 PN 作为一个整体在 OP 发病机制中的作用仍在研究中。本综述全面总结了 PN 在 OP 发病机制中的作用,并进一步探讨了 PN 作为 OP 治疗创新药物靶点的潜力。