Triptolide Inhibits Osteoclast Differentiation and Bone ResorptionIn Vitrovia 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.

Interleukin 6 inhibition by triptolide prevents inflammation in a mouse model of ulcerative colitis

“…Similarly, TL markedly suppressed the overexpression of CCR5 induced by AA. Recently, Xu et al (16) reported that TL inhibited osteoclast differentiation and bone resorption in rheumatoid arthritis, and the repressive effects of T-regulatory cells on bone resorption were enhanced by TL through promoting the secretion of transforming growth factor-β1 and IL-10. A study by Wei et al (19) indicated that TL retarded the Toll-like receptors (TLRs)/nuclear factor (NF)-κB signaling pathway to alleviate experimental colitis.…”

“…TL is known as a drug with marked pharmacological activities, including anti-inflammatory and immunomodulatory properties as well as improvement of the microcirculation; it inhibits the proliferation of various types of cancer cell and enhances tumor sensitivity to chemotherapy (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). In the present study, the expression patterns of IL-6 in a mouse model of UC model were assessed, as well as association between the anti-colitis effects of TL and IL-6 levels.…”

Tripterygium Ingredients for Pathogenicity Cells in Rheumatoid Arthritis

“…So far, research focused on the effects of TwHf on Treg cells in RA were limited. In the co-culture system of bone marrow macrophages and Tregs, TP up-regulated IL-10 and TGF-β1 produced by Treg cells, resulting in the inhibition of osteoclast differentiation and bone resorption ( Xu et al., 2016 ).…”

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

“…In RA, osteoclasts formation and differentiation are closely associated with local bone erosion (Wei et al, ). The previous study has showed that IL‐10 and transforming growth factor‐β1, the cytokines secreted from regulatory T cells, play a key role in suppressing osteoclast differentiation and bone resorption (Xu et al, ). Triptolide enhances these suppressive effects by promoting the production of IL‐10 and transforming growth factor‐β1 (Xu et al, ).…”

“…The previous study has showed that IL‐10 and transforming growth factor‐β1, the cytokines secreted from regulatory T cells, play a key role in suppressing osteoclast differentiation and bone resorption (Xu et al, ). Triptolide enhances these suppressive effects by promoting the production of IL‐10 and transforming growth factor‐β1 (Xu et al, ). The aryl hydrocarbon receptor participates in the activation and differentiation of osteoclasts (Wei et al, ).…”