Isobavachin alleviates hyperuricemia-induced bone loss by GPR35-NLRP3 signal

作者：Xiaolin Cen, Suiqing Mai, Rongrong Huang, Shiqin Lin, Yishuang Chen, Shuqin Zhang, Shuqin Zhang, Pei Zhao, Dong Ming Guo, Xinzhi Liang, Yitao Zhao, Huancun Feng, Zhisheng Xiao, Xinya Lu, Hong Wang, Hong Wang, Denghui Xie, Jianxin Pang, Qun Zhang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.157368 · 被引用次数：1 · 研究领域：Gout, Hyperuricemia, Uric Acid、Inflammasome and immune disorders、Bone health and osteoporosis research

BACKGROUND: GPR35, a member of the G protein-coupled receptor (GPCR) family, promotes osteogenic differentiation and ameliorates inflammation when its expression is enhanced. However, its role in bone homeostasis under hyperuricemia (HUA) conditions remains unexplored, and effective clinical agents for managing osteoporosis comorbid with HUA are scarce. This study aimed to investigate the osteoprotective potential of the GPR35 agonist isobavachin (IBC) against HUA-induced bone loss, focusing on its mechanism involving NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome modulation. METHODS: Bone tissue markers of bone homeostasis and inflammatory infiltration were evaluated in patients with hyperuricemia. To delineate the relationship of HUA, bone homeostasis, and GPR35, osteoblasts (OB) and osteoclasts (OC) were treated with high concentrations of soluble uric acid, in conjunction with label-free cellular assays. The mechanisms underlying the effects of the GPR35 agonist IBC were investigated using molecular docking, in vitro cell culture with IBC treatment, and siRNA-mediated gene silencing. Furthermore, hyperuricemic model mice were established in C57BL/6 J mice to corroborate the bone loss induced by HUA and evaluate the osteoprotective efficacy of IBC. RESULTS: Analysis of bone tissue from HUA patients revealed increased activity of both OB and OC, along with inflammatory cell infiltration. Consistently, in vitro experiments demonstrated tha...