Peng Fushuai, Sun Mingtong, Jing Xingzhi, Chen Fei, Cao Tong, Li Zhenzhen, Li Tao
Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Weiqi Road, Huaiyin District, Jinan, Shandong, 250021, China.
Department of Emergency Surgery, Yidu Central Hospital of Weifang City, Weifang, Shandong, 262500, China.
Mol Med. 2025 Mar 8;31(1):90. doi: 10.1186/s10020-025-01147-z.
Piezo1 is a mechanically sensitive cation channel expressed in various tissues of the human body and has multiple roles in both physiological and pathological processes. However, its role in the occurrence and development of intervertebral disc degeneration (IVDD) is not fully understood.
In the present study, an IVDD mouse model and Piezo1 small interfering (si)RNA was used to investigate the role of Piezo1 in IVDD progression. Furthermore, the Ca inhibitor, BAPTA-AM, and the F-actin cytoskeleton polymerization inhibitor, Latrunculin A, were employed to examine the roles of Ca influx and cytoskeleton dynamics in Piezo1-mediated IVDD progression. Additionally, Yes-associated protein (Yap) small interfering (si)RNA was used to investigate the involvement of Yap in Piezo1-induced IVDD progression.
The findings of the present study indicated that Piezo1 was positively associated with IVDD and that Piezo1 upregulation promoted IVDD via facilitating cartilage endplate (CEP) degeneration and calcification. The Ca inhibitor, BAPTA-AM, and the F-actin cytoskeleton polymerization inhibitor, Latrunculin A, inhibited Piezo1-mediated extracellular matrix degradation and CEP chondrocyte degeneration. Moreover, it was found that Piezo1 activated Yap through an F-actin-mediated non-canonical pathway and that Yap siRNA inhibited Piezo1 upregulation-induced IVDD progression.
Overall, the results of the present study indicate that increased expression of Piezo1 is closely related to the occurrence and development of IVDD and that the Piezo1-mediated Ca/F-actin/Yap axis contributes to this process. Thus, targeting Piezo1 may provide a new strategy for the treatment of IVDD.
Piezo1是一种在人体各种组织中表达的机械敏感阳离子通道，在生理和病理过程中具有多种作用。然而，其在椎间盘退变（IVDD）发生发展中的作用尚未完全明确。
在本研究中，使用IVDD小鼠模型和Piezo1小干扰（si）RNA来研究Piezo1在IVDD进展中的作用。此外，采用钙抑制剂BAPTA-AM和F-肌动蛋白细胞骨架聚合抑制剂Latrunculin A，以研究钙内流和细胞骨架动力学在Piezo1介导的IVDD进展中的作用。另外，使用Yes相关蛋白（Yap）小干扰（si）RNA来研究Yap在Piezo1诱导的IVDD进展中的参与情况。
本研究结果表明，Piezo1与IVDD呈正相关，且Piezo1上调通过促进软骨终板（CEP）退变和钙化来促进IVDD。钙抑制剂BAPTA-AM和F-肌动蛋白细胞骨架聚合抑制剂Latrunculin A抑制了Piezo1介导的细胞外基质降解和CEP软骨细胞退变。此外，发现Piezo1通过F-肌动蛋白介导的非经典途径激活Yap，且Yap siRNA抑制了Piezo1上调诱导的IVDD进展。
总体而言，本研究结果表明Piezo1表达增加与IVDD的发生发展密切相关，且Piezo1介导的Ca/F-肌动蛋白/Yap轴促成了这一过程。因此，靶向Piezo1可能为IVDD的治疗提供一种新策略。
