Ras homolog gene family member A (RhoA) plays a major role in the Wnt/planar cell polarity (PCP) pathway, which is significantly activated in patients with rheumatoid arthritis (RA). The function of RhoA in RA synovitis and bone erosion is still elusive. Here, we not only explored the impact of RhoA on the proliferation and invasion of RA fibroblast-like synoviocytes (FLSs) but also elucidated its effect on mouse osteoclast and a mouse model of collagen-induced arthritis (CIA). Results showed that RhoA was overexpressed in RA and CIA synovial tissues. Lentivirus-mediated silencing of RhoA increased apoptosis, attenuated invasion, and dramatically upregulated osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) ratio in RA-FLSs. Additionally, the silencing of RhoA inhibited mouse osteoclast differentiation in vitro and alleviated synovial hyperplasia and bone erosion in the CIA mouse model. These effects in RA-FLSs and osteoclasts were all regulated by RhoA/Rho-associated protein kinase 2 (ROCK2) and might interact with Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways.

中文翻译：

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RhoA 通过 Wnt/PCP 通路促进类风湿性关节炎的滑膜增殖和骨侵蚀

Ras 同源基因家族成员 A (RhoA) 在 Wnt/平面细胞极性 (PCP) 通路中发挥重要作用，该通路在类风湿性关节炎 (RA) 患者中显着激活。RhoA 在 RA 滑膜炎和骨侵蚀中的功能仍不清楚。在这里，我们不仅探讨了 RhoA 对 RA 成纤维样滑膜细胞 (FLS) 增殖和侵袭的影响，而且阐明了其对小鼠破骨细胞和胶原诱导性关节炎 (CIA) 小鼠模型的影响。结果显示，RhoA 在 RA 和 CIA 滑膜组织中过表达。慢病毒介导的 RhoA 沉默可增加 RA-FLS 中的细胞凋亡、减弱侵袭，并显着上调 RA-FLS 中骨保护素/核因子κ B 受体激活剂配体 (OPG/RANKL) 的比例。此外，RhoA 沉默可抑制体外小鼠破骨细胞分化，并减轻 CIA 小鼠模型中的滑膜增生和骨侵蚀。RA-FLS 和破骨细胞中的这些作用均受 RhoA/Rho 相关蛋白激酶 2 (ROCK2) 调节，并可能与 Janus 激酶/信号转导器和转录激活剂 (JAK/STAT) 通路相互作用。