Department of Orthopedics, The Affiliated People's Hospital with Jiangsu University, 8 Dianli Road, Runzhou District, Zhenjiang City, 212002, Jiangsu Province, China.
Department of Stomatology, The Affiliated Hospital with Jiangsu University, 8 Jiefang Road, Jingkou District, Zhenjiang City, 212002, Jiangsu Province, China.
J Orthop Surg Res. 2023 Oct 18;18(1):784. doi: 10.1186/s13018-023-04207-4.
Osteoarthritis (OA) is a frequently encountered debilitating joint disorder. Whether plexin C1 (PLXNC1) is implicated in OA is far from being investigated despite its well-documented pro-inflammatory property in human diseases. The goal of this study is to expound the specific role of PLXNC1 in OA and elaborate the probable action mechanism.
Firstly, PLXNC1 expression in the cartilage tissues of patients with OA was examined with GEO database. In interleukin-1beta (IL-1β)-induced OA cell model, RT-qPCR and western blotting tested the expression of PLXNC1, glucose-regulating protein 78 (GRP78) and extracellular matrix (ECM) degradation-related factors. Cell viability and inflammation were respectively judged by CCK-8 assay and RT-qPCR. TUNEL and western blotting estimated cell apoptosis. The potential binding between PLXNC1 and GRP78 was corroborated by Co-IP assay. Western blotting also tested the expression of endoplasmic reticulum stress (ERS)-associated proteins.
As it turned out, PLXNC1 expression was elevated in the cartilage tissues of patients with OA and IL-1β-treated chondrocytes. When PLXNC1 was depleted, the viability injury, inflammation, apoptosis and ECM degradation of chondrocytes exposed to IL-1β were obstructed. Besides, GRP78 bond to PLXNC1 in IL-1β-treated chondrocytes. The ascending GRP78 expression in the chondrocytes exposed to IL-1β was depleted after PLXNC1 was silenced. Meanwhile, the impacts of PLXNC1 deficiency on the viability, inflammatory response, apoptosis, ECM degradation as well as ERS in IL-1β-exposed chondrocytes were abolished by GRP78 up-regulation.
In summary, PLXNC1 silencing might interact with and down-regulate GRP78 to mitigate the apoptosis, inflammation, and ECM degradation of IL-1β-insulted chondrocytes in OA.
骨关节炎（OA）是一种常见的使人虚弱的关节疾病。尽管 plexin C1（PLXNC1）在人类疾病中有明确的促炎作用，但它是否与 OA 有关仍有待研究。本研究的目的是阐述 PLXNC1 在 OA 中的特定作用，并阐述可能的作用机制。
首先，利用 GEO 数据库检测 OA 患者软骨组织中 PLXNC1 的表达。在白细胞介素-1β（IL-1β）诱导的 OA 细胞模型中，通过 RT-qPCR 和 Western blot 检测 PLXNC1、葡萄糖调节蛋白 78（GRP78）和细胞外基质（ECM）降解相关因子的表达。通过 CCK-8 测定和 RT-qPCR 分别判断细胞活力和炎症。TUNEL 和 Western blot 估计细胞凋亡。通过 Co-IP 测定证实 PLXNC1 与 GRP78 之间的潜在结合。Western blot 还检测了内质网应激（ERS）相关蛋白的表达。
结果表明，OA 患者软骨组织和 IL-1β 处理的软骨细胞中 PLXNC1 表达升高。沉默 PLXNC1 后，IL-1β 处理的软骨细胞活力损伤、炎症、凋亡和 ECM 降解受到抑制。此外，GRP78 在 IL-1β 处理的软骨细胞中与 PLXNC1 结合。沉默 PLXNC1 后，IL-1β 处理的软骨细胞中 GRP78 表达升高。同时，上调 GRP78 可消除 PLXNC1 缺失对 IL-1β 暴露软骨细胞活力、炎症反应、凋亡、ECM 降解和 ERS 的影响。
综上所述，沉默 PLXNC1 可能与下调 GRP78 相互作用，减轻 OA 中 IL-1β 损伤的软骨细胞凋亡、炎症和 ECM 降解。
