Chondrocytes constantly receive external stimuli, which regulates remodeling. An optimal level of mechanical stress is essential for maintaining chondrocyte homeostasis, however, excessive mechanical stress induces inflammatory cytokines and protease, such as matrix metalloproteinases (MMPs). Therefore, excessive mechanical stress is considered to be one of the main causes to cartilage destruction leading to osteoarthritis (OA). Integrins are well‐known as cell adhesion molecules and act as receptors for extracellular matrix (ECM), and are believed to control intracellular signaling pathways both physically and chemically as a mechanoreceptor. However, few studies have focused on the roles and functions of integrins in inflammation caused by excessive mechanical stress. In this study, we examined the relationship between integrins (αVβ3 and αVβ5) and the expression of inflammatory factors under mechanical loading in chondrocytes by using an integrin receptor antagonist (cilengitide). Cilengitide suppressed the gene expression of interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), matrix metalloproteinase‐3 (MMP‐3), and MMP‐13 induced by excessive mechanical stress. In addition, the protein expression of IL1‐β and MMP‐13 was also inhibited by the addition of cilengitide. Next, we investigated the involvement of intracellular signaling pathways in stress‐induced integrin signaling in chondrocytes by using western blotting. The levels of p‐FAK, p‐ERK, p‐JNK, and p‐p38 were enhanced by excessive mechanical stress and the enhancement was suppressed by treatment with cilengitide. In conclusion, this study revealed that excessive mechanical stress may activate integrins αVβ3 and αVβ5 on the surface of chondrocytes and thereby induce an inflammatory reaction by upregulating the expression of IL‐1β, TNF‐α, MMP‐3, and MMP‐13 through phosphorylation of FAK and MAPKs.

中文翻译：

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西仑吉肽对过度机械应力下软骨细胞炎症的保护作用

软骨细胞不断受到外部刺激，从而调节重塑。最佳水平的机械压力对于维持软骨细胞的动态平衡至关重要，但是，过度的机械压力会引起炎症性细胞因子和蛋白酶，例如基质金属蛋白酶（MMP）。因此，过度的机械应力被认为是导致软骨破坏导致骨关节炎（OA）的主要原因之一。整联蛋白是众所周知的细胞粘附分子，并充当细胞外基质（ECM）的受体，并且据信可以作为机械受体来物理和化学地控制细胞内信号传导途径。但是，很少有研究集中于整联蛋白在过度机械应力引起的炎症中的作用和功能。在这个研究中，我们通过使用整合素受体拮抗剂（西仑吉肽）研究了软骨素在机械负荷下整合素（αVβ3和αVβ5）与炎症因子表达之间的关系。西仑吉肽抑制过高机械应力诱导的白介素-1β（IL-1β），肿瘤坏死因子-α（TNF-α），基质金属蛋白酶-3（MMP-3）和MMP-13的基因表达。此外，加入西仑吉肽也可抑制IL1-β和MMP-13的蛋白表达。接下来，我们通过蛋白质印迹研究了细胞内信号通路在应激诱导的软骨细胞整合素信号传导中的参与。过度的机械应力会增强p-FAK，p-ERK，p-JNK和p-p38的水平，而西仑吉肽治疗则会抑制这种增强。结论，