Compressive stress induces spinal vertebral growth plate chondrocytes apoptosis via Piezo1
Compressive stress induces spinal vertebral growth plate chondrocytes apoptosis via Piezo1
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DOI：
10.1002/jor.25527
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发表时间：
2023-02-14
影响因子：
2.8
通讯作者：
Jing, Xingzhi
中科院分区：
文献类型：
--
作者：
Chen, Fei;Sun, Mingtong;Jing, Xingzhi
许多临床研究表明生物力学因素与青少年特发性脊柱侧凸（AIS）的发病率和病理进展之间存在相关性。但目前对AIS的研究主要集中在病因学方面，很少有研究报道AIS进行性加重的原因。在本研究中，我们的目的是研究Piezo1在压缩应力诱导的小鼠脊柱椎骨生长板软骨细胞凋亡中的作用。首先，建立小鼠脊柱侧凸模型，观察Piezo1在脊柱侧凸模型中的表达及细胞凋亡的程度。我们发现脊柱侧凸小鼠椎体生长板凹侧Piezo1的表达和凋亡程度明显高于凸侧。进一步分离脊柱椎骨生长板软骨细胞，并用Yoda 1处理以模拟Piezo 1过载。过量的Piezo1显著促进脊椎生长板软骨细胞的凋亡。此外，静态气体压应力被用来模拟在脊柱侧凸的过程中增加的凹形压应力，有或没有GsMTx4，一种压电抑制剂。观察到随着静态压应力的增加，Piezo1的表达增加，Piezo1抑制剂GsMTx4处理的椎骨生长板软骨细胞减弱了上述现象。总之，我们的研究结果表明，压应力通过诱导Piezo1的不同表达与脊柱侧凸椎体生长板凸侧和凹侧的不同程度的细胞凋亡密切相关。降低椎体生长板凹侧Piezo1的表达，抑制凹侧椎体不对称应力引起的双侧椎体生长板软骨细胞凋亡，可能是AIS有前景的治疗策略。
Many clinical studies have indicated an association between biomechanical factors and the incidence and pathological progression of adolescent idiopathic scoliosis (AIS). However, at present, the research on AIS is mainly focused on the etiology, and there are few studies reporting the causes of progressive aggravation of AIS. In the present study, we aim to investigate the role of Piezo1 in compressive stress-induced mouse spinal vertebral growth plate chondrocytes apoptosis. First, a scoliosis mouse model was established, and the expression of Piezo1 as well as the degree of apoptosis were investigated. We found that the expression of Piezo1 and the degree of apoptosis were significantly higher on the concave sides than that on the convex sides of the vertebral growth plate in mice with scoliosis. Spinal vertebral growth plate chondrocytes were further isolated and treated with Yoda1 to mimic Piezo1 overload. Excess Piezo1 significantly promoted apoptosis of spinal vertebral growth plate chondrocytes. Moreover, static gas compressive stress was used to simulate the increased concave compressive stress in the process of scoliosis with or without GsMTx4, a Piezo inhibitor. It was observed that with the increase of static compressive stress, the expression of Piezo1 increased, and the chondrocytes of vertebral growth plate treated with Piezo1 inhibitor GsMTx4 weakened the above phenomena. In conclusion, our results indicated that compressive stress is strongly associated with the different degrees of apoptosis on both sides on the convex and concave sides of the vertebral growth plate in scoliosis via inducing different expressions of Piezo1. Reducing the expression of Piezo1 in the concave side of the vertebral growth plate and inhibiting the apoptosis of chondrocytes in the bilateral vertebral growth plate caused by asymmetric stress on both sides of the concave vertebral body may be a promising treatment strategy for AIS.