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

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 des...

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Published inChinese medicine Vol. 18; no. 1; p. 54
Main Authors Peng, Qiuwei, Wang, Jian, Han, Man, Zhao, Minghong, Li, Kesong, Lu, Tianming, Guo, Qiuyan, Jiang, Quan
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 15.05.2023
BioMed Central
BMC
Subjects
Apoptosis
Arthritis
Bone loss
Cell cycle
Drugs
Enzymatic activity
Enzymes
Ethylenediaminetetraacetic acid
Inflammation
Joint diseases
L-Lactate dehydrogenase
Lactate dehydrogenase
Medical research
Molecular modelling
Osteoclast
Osteoclastogenesis
Osteoclasts
Penicillin
Reactive oxygen species
Rheumatoid arthritis
Rheumatoid factor
Tanshinone IIA
Tanshinones
China
Beijing China
United States > US
Tanshinone IIA
Lactate dehydrogenase
Reactive oxygen species
Osteoclast
Rheumatoid arthritis
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Summary: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.
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ISSN:1749-8546
1749-8546
DOI:10.1186/s13020-023-00765-1