Triptolide prevents osteoarthritis via inhibiting hsa-miR-20b
- 45 Downloads
Triptolide has been widely reported to exhibit potential therapeutic value in multiple inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Although its safety and efficacy as an anti-inflammatory agent have been verified by many studies, the effect of triptolide on osteoarthritis (OA) was not clearly understood. In this study, we found that triptolide prevented OA development in a surgical destabilization of the medial meniscus (DMM) mouse model. In addition, triptolide inhibited both DMM-induced and LPS-induced expression of pro-inflammatory cytokines in the human monocytic cell line THP-1. Further mechanistic studies showed that the reduction of pro-inflammatory cytokines by triptolide was mediated by the upregulation of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) and downregulation of caspase-1. Finally, we identified that hsa-miR-20b, a microRNA targeting the NLRP3 gene, was downregulated by triptolide. This study provides a novel insight into the effect on triptolide in preventing OA pathogenesis.
KeywordsTriptolide Osteoarthritis NLRP3 hsa-miR-20b
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M (2015) NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol 4:296–307. https://doi.org/10.1016/j.redox.2015.01.008 CrossRefPubMedPubMedCentralGoogle Scholar
- Hang LH, Li SN, Shao DH, Chen Z, Chen YF, Shu WW (2014) Evidence for involvement of spinal RANTES in the antinociceptive effects of triptolide, a diterpene triepoxide, in a rat model of bone cancer pain. Basic Clin Pharmacol Toxicol 115:477–480. https://doi.org/10.1111/bcpt.12265 CrossRefPubMedGoogle Scholar
- Li Y, Yu C, Zhu WM, Xie Y, Qi X, Li N, Li JS (2010) Triptolide ameliorates IL-10-deficient mice colitis by mechanisms involving suppression of IL-6/STAT3 signaling pathway and down-regulation of IL-17. Mol Immunol 47:2467–2474. https://doi.org/10.1016/j.molimm.2010.06.007 CrossRefPubMedGoogle Scholar
- Zeng R, Zeng L, Chen Y, Zhao F, Li R, Wen L, Zhang C (2011) Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro. J Huazhong Univ Sci Technol Med Sci31:446–451 https://doi.org/10.1007/s11596-011-0471-7