Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and secondary osteogenesis. It has been previously demonstrated that the CCAL1 locus is the gene encoding tumor necrosis factor receptor superfamily member 11B (TNFRSF11B). The purpose of this study was to demonstrate the role of CCAL1 in OA progression and to elucidate its molecular mechanisms. We report that CCAL1 is highly expressed in the cartilage of OA patients and its expression level is positively correlated with the severity of OA. We found that CCAL1 causes a switch to the fibrosis‐prone phenotype of Human Chondrocyte‐Osteoarthritis (HC‐OA) cells. In addition, CCAL1 enhances cell viability and promotes the proliferation of HC‐OA cells. Finally, the detection of proteins associated with the NF‐κB/AMPK signaling pathway by western blot suggested that CCAL1 exerts its role on HC‐OA cells by activating the NF‐κB signaling pathway and inhibiting the AMPK signaling pathway, which was verified through the addition of NF‐κB inhibitor caffeic acid phenethyl ester (CAPE) and AMPK activator 5‐aminoimidazole‐4‐carboxamide riboside (AICAR). In summary, we report that CCAL1 may promote OA through the NF‐κB and AMPK signaling pathways.

中文翻译：

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CCAL1通过NF-κB/AMPK信号通路增强骨关节炎

骨关节炎（OA）是一种慢性关节疾病，其特征是关节软骨退变和继发性成骨。先前已经证明，CCAL1 基因座是编码肿瘤坏死因子受体超家族成员 11B（TNFRSF11B）。本研究的目的是证明 CCAL1 在 OA 进展中的作用并阐明其分子机制。我们报告 CCAL1 在 OA 患者的软骨中高表达，其表达水平与 OA 的严重程度呈正相关。我们发现 CCAL1 导致人类软骨细胞 - 骨关节炎 (HC-OA) 细胞向纤维化倾向表型的转变。此外，CCAL1 可增强细胞活力并促进 HC-OA 细胞的增殖。最后，通过蛋白质印迹检测与 NF-κB/AMPK 信号通路相关的蛋白质表明 CCAL1 通过激活 NF-κB 信号通路和抑制 AMPK 信号通路对 HC-OA 细胞发挥作用，这通过添加 NF-κB 抑制剂咖啡酸苯乙酯 (CAPE) 和 AMPK 激活剂 5-氨基咪唑-4-甲酰胺核苷 (AICAR) 得到验证。总之，我们报告说 CCAL1 可能通过 NF-κB 和 AMPK 信号通路促进 OA。