Periostin promotes nucleus pulposus cells apoptosis by activating the Wnt/β‐catenin signaling pathway

作者：Daxue Zhu, Zhaoheng Wang, Guangzhi Zhang, Congwen Ma, Xiaoming Qiu, Yidian Wang, Mingqiang Liu, Xudong Guo, Haiwei Chen, Qiang Deng, Xuewen Kang · 发表于：The FASEB Journal · 年份：2022 · DOI：10.1096/fj.202200123r · 被引用次数：32 · 研究领域：Spine and Intervertebral Disc Pathology、Musculoskeletal pain and rehabilitation、Cervical and Thoracic Myelopathy

Intervertebral disc (IVD) degeneration (IVDD) is closely linked to degenerative spinal disease, resulting in disability, poor quality of life, and financial burden. Apoptosis of nucleus pulposus (NP) cells (NPCs) is a key pathological basis of IVDD. Periostin (POSTN), an extracellular matrix protein, is expressed in many tissues, whereas its abnormal expression is associated with IVDD. The conventional Wnt/β-catenin pathway is also involved in IVDD and contributes to NPCs apoptosis. However, research on the mechanisms of POSTN in IVDD is lacking. This study investigated the relationship between POSTN and β-catenin expression in degenerated IVDs. We detected the expression of POSTN, β-catenin, and cleaved-caspase-3 (C-caspase3) in degenerated and non-degenerated IVD tissues of different grades (n = 8) using RT-qPCR, immunohistochemical staining, and western blotting analysis. Next, we explored the effects of recombinant periostin (rPOSTN) and isoquercitrin (Iso), an inhibitor of the Wnt/β-catenin pathway, on NPCs apoptosis. Finally, we inhibited the expression of POSTN in degenerated NPCs in vivo and investigated the anti-apoptotic effect. The expression of β-catenin, POSTN, and C-caspase3 in severe degenerative IVDs was significantly higher than that in mild degenerative IVDs. These findings were confirmed in rat and cell-based degenerative models. When treated with rPOSTN, the Wnt/β-catenin pathway activity and cell apoptosis were time- and dose-dependent. However, rPOSTN-in...