The triptolide-induced apoptosis of osteoclast precursor by degradation of cIAP2 and treatment of rheumatoid arthritis of TNF-transgenic mice.

Abstract

This study aims to discuss the effect of triptolide (TPL) on rheumatoid arthritis (RA) and the mechanism related to osteoclast precursor (OCP) and osteoclast (OC). TNF-transgenic RA mice were treated with different doses of TPL by gavage. After the administration was finished, the curative effects were evaluated and compared, and the OCP apoptosis rates, the OC number, and the OC differentiation ability in vitro were detected. Finally, splenocytes of wild-type mice were cultured in vitro and induced to differentiate into OCP, and the cell apoptosis rate, cIAP2, and apoptotic effectors expression level were detected after cIAP2 overexpression and TPL administration. After TPL administration, the RA symptoms in the TPL groups were all better, the apoptosis rate of OCP was higher, and the amount of OC in vitro were lower than that in the control group (all P < 0.05), and all of the changes in the high-dose group were more obvious than the low-dose group. In splenocytes cells cultured in vitro, cIAP2 overexpression could decrease the apoptosis rate of OCPs and increase the OC number, and TPL treatment could down-regulate the cIAP2 and promote OCP apoptosis and OC reduction. In conclusion, TPL could induce OCP apoptosis and inhibit OC formation to effectively treat RA by mediating cIAP2 degradation.

• Authors: Shengli Wang, Zhigang Liu, Jingchun Wang, Yifei Wang, Jianhua Liu, Xinying Ji, Xinchun Wang
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 33 Issue 2 Pg. 342-349 (Feb 2019) ISSN: 1099-1573 [Electronic] England
• PMID: 30417444 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons, Ltd.

Chemical References

• Diterpenes
• Epoxy Compounds
• Phenanthrenes
• Tumor Necrosis Factor-alpha
• triptolide
• Baculoviral IAP Repeat-Containing 3 Protein

Topics

• Adult Stem Cells (drug effects, physiology)
• Animals
• Apoptosis (drug effects)
• Arthritis, Rheumatoid (drug therapy, genetics, metabolism, pathology)
• Baculoviral IAP Repeat-Containing 3 Protein (metabolism)
• Diterpenes (pharmacology)
• Epoxy Compounds (pharmacology)
• HEK293 Cells
• Humans
• Mice
• Mice, Transgenic
• Osteoclasts (drug effects, pathology, physiology)
• Phenanthrenes (pharmacology)
• Proteolysis (drug effects)
• Tumor Necrosis Factor-alpha (genetics)