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- Title
Tanshinone IIA inhibits osteoclastogenesis in rheumatoid arthritis via LDHC-regulated ROS generation.
- Authors
Peng, Qiuwei; Wang, Jian; Han, Man; Zhao, Minghong; Li, Kesong; Lu, Tianming; Guo, Qiuyan; Jiang, Quan
- Abstract
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.
- Subjects
BIOLOGICAL models; IN vitro studies; OSTEOCLASTS; ANIMAL experimentation; ONE-way analysis of variance; RATS; RHEUMATOID arthritis; RESEARCH funding; REACTIVE oxygen species; PLANT extracts
- Publication
Chinese Medicine, 2023, Vol 18, Issue 1, p1
- ISSN
1749-8546
- Publication type
Article
- DOI
10.1186/s13020-023-00765-1