Department of Orthopaedics, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang, China.
Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Biomed Res Int. 2022 Jul 13;2022:7250578. doi: 10.1155/2022/7250578. eCollection 2022.
A balance between osteoblasts and osteoclasts is essential to maintain skeletal integrity, regulating bone metabolism and bone remodeling. The nucleotide binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome is known as a cytosolic complex involved in producing proinflammatory cytokines consisting of interleukin- (IL-) 1, which accelerates the occurrence of osteoporosis. Therefore, we aimed to investigate the effect of a novel NLRP3 inhibitor INF 39 on bone formation and bone resorption. . Cell viability of INF 39-treated osteoclasts and calvarial osteoblasts was tested by CCK-8 assays. Quantitative RT-PCR (qRT-PCR) was used to evaluate gene expression level during osteoblast and osteoclast formation. Western blot analysis was used to determine the effect of INF 39 on osteogenic and osteoclast-related proteins.
It was shown that INF 39 promotes osteoblast differentiation via inhibiting NLRP3, thereby reducing the production of IL-1 dependent on NLRP3 . However, RANKL-induced osteoclast differentiation is not influenced by INF 39 .
Our study suggests that NLRP3 could be a new target and INF 39 may be a potential option for prevention and treatment of osteoporosis.
成骨细胞和破骨细胞之间的平衡对于维持骨骼完整性至关重要，它调节着骨代谢和骨重塑。核苷酸结合寡聚化结构域、富含亮氨酸重复序列和pyrin 结构域蛋白 3（NLRP3）炎症小体是一种胞质复合物，已知其参与产生包括白细胞介素（IL）-1 在内的促炎细胞因子，从而加速骨质疏松的发生。因此，我们旨在研究新型 NLRP3 抑制剂 INF 39 对骨形成和骨吸收的影响。通过 CCK-8 测定法检测 INF 39 处理的破骨细胞和成颅骨细胞的细胞活力。采用定量 RT-PCR（qRT-PCR）评估成骨细胞和破骨细胞形成过程中的基因表达水平。采用 Western blot 分析确定 INF 39 对成骨和破骨相关蛋白的影响。结果表明，INF 39 通过抑制 NLRP3 促进成骨细胞分化，从而减少依赖 NLRP3 的 IL-1 的产生。然而，INF 39 不影响 RANKL 诱导的破骨细胞分化。结论：我们的研究表明，NLRP3 可能成为一个新的靶点，INF 39 可能是预防和治疗骨质疏松症的一种潜在选择。
