Lin Naikai, Song Zehui, Ma Bitao, Wang Peng
Department of Orthopedics, Hangzhou Yuhang District First People's Hospital, Zhejiang, China.
Department of Traditional Chinese Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Connect Tissue Res. 2025 May;66(3):190-203. doi: 10.1080/03008207.2025.2487470. Epub 2025 Apr 10.
We probed the roles of SNHG7, miR-146b, PCBP1, and IL-β in the development of osteoarthritis (OA).
OA models were established using anterior cruciate ligaments, and chondrocytes were obtained from mouse cartilage tissue. Cells were treated with 10 ng/ml Il-1β. RT-qPCR was used to detect the expression of SNHG7, miR-146b, PCBP1, and IL-β in tissues and cells. Safranin-O/Fast Green staining was performed to analyze the cartilage damage in each group of mice.
SNHG7 and PCBP1 expressions were down-regulated, and miR-146b expression was up-regulated in OA tissue and IL-1β-treated chondrocytes compared to normal cartilage tissue and chondrocytes. Forced SNHG7 expression improved cartilage structure, enhanced proliferative viability of chondrocytes, and inhibited apoptosis and IL-1β release in IL-1β-treated chondrocytes in OA mice. In contrast, miR-146b upregulation decreased proliferative viability and promoted apoptosis and IL-1β release in chondrocytes. Rescue assays showed that miR-146b attenuated the protective effects of SNHG7 on apoptosis and inflammation in IL-1β-treated chondrocytes, and activation of PCBP1 expression significantly inhibited the cytotoxic effects of miR-146b. Mechanistically, SNHG7 acted as a competitive endogenous RNA by targeting miR-146b to promote the expression of PCBP1.
This study confirms that SNHG7 inhibits IL-1β-mediated inflammatory responses in chondrocytes via the miR-146b/PCBP1 axis, thereby suppressing IL-1β-induced OA.
我们探究了SNHG7、miR-146b、PCBP1和白细胞介素-β（IL-β）在骨关节炎（OA）发展过程中的作用。
使用前交叉韧带建立OA模型，并从小鼠软骨组织中获取软骨细胞。细胞用10 ng/ml的IL-1β处理。采用逆转录-定量聚合酶链反应（RT-qPCR）检测组织和细胞中SNHG7、miR-146b、PCBP1和IL-β的表达。进行番红O/固绿染色以分析每组小鼠的软骨损伤情况。
与正常软骨组织和软骨细胞相比，OA组织及IL-1β处理的软骨细胞中SNHG7和PCBP1表达下调，miR-146b表达上调。在OA小鼠中，强制表达SNHG7可改善软骨结构，增强软骨细胞的增殖活力，并抑制IL-1β处理的软骨细胞的凋亡及IL-1β释放。相反，上调miR-146b可降低软骨细胞的增殖活力，促进其凋亡及IL-1β释放。挽救实验表明，miR-146b减弱了SNHG7对IL-1β处理的软骨细胞凋亡和炎症的保护作用，而激活PCBP1表达可显著抑制miR-146b的细胞毒性作用。机制上，SNHG7通过靶向miR-146b作为竞争性内源性RNA来促进PCBP1的表达。
本研究证实SNHG7通过miR-146b/PCBP1轴抑制软骨细胞中IL-1β介导的炎症反应，从而抑制IL-1β诱导的OA。
