Tanshinone IIA inhibits osteoclastogenesis in rheumatoid arthritis via LDHC-regulated ROS generation

Chinese Medicine

Research

Qiuyan Guo¹  Jian Wang²  Man Han²  Quan Jiang²  Qiuwei Peng²  Kesong Li²  Tianming Lu³  Minghong Zhao⁴ 

[1] Artemisnin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China;Department of Rheumatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, 100053, Beijing, China;School of Public Health, Guangxi Medical University, 530021, Guangxi, China;The First School of Clinical Medicine, Gannan Medical University, 341000, Ganzhou, China;

关键词: Tanshinone IIA;    Rheumatoid arthritis;    Osteoclast;    Lactate dehydrogenase;    Reactive oxygen species;   

DOI  :  10.1186/s13020-023-00765-1

 received in 2023-03-29, accepted in 2023-05-05,  发布年份 2023

来源: Springer

【 摘 要 】

Rheumatoid arthritis (RA) is characterized by bone destruction in the afflicted joints, and during the process of bone destruction, osteoclasts play a crucial role. Tanshinone IIA (Tan IIA) has shown anti-inflammatory effects in RA. However, the exact molecular mechanisms by which it delays bone destruction remain largely unexplained. Here, we found that Tan IIA decreased the severity of and ameliorated bone loss in an AIA rat model. In vitro, Tan IIA inhibited RANKL-induced osteoclast differentiation. By activity-based protein analysis (ABPP) combined with LC‒MS/MS, we discovered that Tan IIA covalently binds to the lactate dehydrogenase subunit LDHC and inhibits its enzymatic activity. Moreover, we found that Tan IIA inhibits the generation of osteoclast-specific markers by reducing the accumulation of reactive oxygen species (ROS), thus reducing osteoclast differentiation. Finally, our results reveal that Tan IIA suppresses osteoclast differentiation via LDHC-mediated ROS generation in osteoclasts. Tan IIA can thus be regarded as an effective drug for the treatment of bone damage in RA.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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