title: Triptolide Inhibits Osteoclast Differentiation and Bone Resorption In Vitro via Enhancing the Production of IL-10 and TGF-β1 by Regulatory T Cells.
abstract: Triptolide, a purified component of Tripterygiumwilfordii Hook F, has been shown to have immunosuppressive and anti-inflammatory properties in rheumatoid arthritis (RA). Although triptolide has demonstrated that it could suppress bone destruction in collagen-induced mice, its therapeutic mechanism remains unclear. Many studies have investigated the effect of triptolide on Tregs and Tregs-related cytokine involved in RA. Additionally, previous studies have implied that Tregs inhibit osteoclast differentiation and bone resorption. Thus, in this study we aimed to explore the regulatory mechanism by which triptolide influences the Treg-mediated production of IL-10 and TGF-β1 to affect osteoclast differentiation and bone resorption. In cocultures system of Tregs and mouse bone marrow macrophages (BMMs), Tregs inhibited the differentiation of osteoclasts and reduced the resorbed areas significantly and the production of both IL-10 and TGF-β1 was upregulated. When the coculture systems were pretreated with triptolide, they produced higher levels of IL-10 and TGF-β1. Our data indicate that triptolide enhances the suppressive effects of Tregs on osteoclast differentiation and bone resorption by enhancing the secretion of IL-10 and TGF-β1. Tregs are most likely involved in the triptolide-mediated regulation of bone metabolism and may provide a potential therapeutic target for the treatment of inflammatory bone destruction.
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China; Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Institute of Basic Theory of Chinese Medicine, China Academy of Chinese Medical Science, Beijing 100700, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing 100700, China.
authors.forename: Cheng
authors.identifier: 0000-0002-6474-9198
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institute of Clinical Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
authors.forename: Qi
authors.identifier: 0000-0001-7756-7134
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China; Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China; Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Beijing University of Chinese Medicine, Beijing 100029, China; Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Guo
authors.affiliation: Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing 100700, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Cheng
authors.identifier: 0000-0002-5601-9670
authors.initials: C
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects*; D018920:Coculture Techniques; D003094:Collagen / Q000737:chemistry; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016753:Interleukin-10 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology*; D010616:Phenanthrenes / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D004852:Epoxy Compounds; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D010616:Phenanthrenes; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; C001899:triptolide; D003094:Collagen; D000071681:Tartrate-Resistant Acid Phosphatase