Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-қB activation and titanium particle-induced osteolysis in a mouse model

Huang, Jianbin; Zhou, Lin; Wu, Huafei; Pavlos, Nathan J.; Chim, Shek Man; Liu, Qian; Zhao, Jinmin; Wang, Xue; Tan, Ren Xiang; Ye, Ji-Ming; Xu, Jing; Ang, Estabelle S.M.; Feng, Haotian; Tickner, Jennifer; Xu, Jiake; Ding, Yue

doi:10.1016/j.mce.2014.10.016

Cited by 39 publications

(27 citation statements)

References 31 publications

(40 reference statements)

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“…Additional support for targeting RANK/RANKL arrives from studies demonstrating inhibition of osteolysis by: treatment with methotrexate, 95 ursolic acid, 96 and triptolide 97 (RANKL-mediated), p38 suppression 98 (downstream signaling cascade induced by RANKL), and RANK small interfering RNA local injection. 99 Methotrexate is an interesting option in that its effects are mainly mediated by the adenosine A 2A receptor, which has many downstream effects.…”

Section: Treatmentmentioning

confidence: 99%

A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response

et al. 2016

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In a world where increasing joint arthroplasties are being performed on increasingly younger patients, osteolysis as the leading cause of failure after total joint arthroplasty (TJA) has gained considerable attention. Ultra-high molecular weight polyethylene wear-induced osteolysis is the process by which prosthetic debris mechanically released from the surface of prosthetic joints induces an immune response that favors bone catabolism, resulting in loosening of prostheses with eventual failure or fracture. The immune response initiated is innate in that it is nonspecific and self-propagating, with monocytic cells and osteoclasts being the main effectors. To date, detecting disease early enough to implement effective intervention without unwanted systemic side effects has been a major barrier. These barriers can be overcome using newer in vivo imaging techniques and modules linked with fluorescence and/or chemotherapies. We discuss the pathogenesis of osteolysis, and provide discussion of the challenges with imaging and therapeutics. We describe a positron emission tomography imaging cinnamoyl-Phe-(D)-Leu-Phe-(D)-Leu-Phe-Lys module, specific to macrophages, which holds promise in early detection of disease and localization of treatment. Further research and increased collaboration among therapeutic and three-dimensional imaging researchers are essential in realizing a solution to clinical osteolysis in TJA.

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Section: Treatmentmentioning

confidence: 99%

A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response

et al. 2016

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“…In search for natural compounds that can inhibit osteolysis, we have conducted drug screening using combined osteoclastogenesis assays, and NF-κB and NFAT luciferase reporter gene assays. To this end, we have identified novel compounds that inhibit osteoclast formation and osteolysis [ 13 , 14 ]. In this study, we found that berberine sulfate, a derivative formula of unsulfated berberine that is easily absorbed, inhibits osteoclast differentiation.…”

Section: Introductionmentioning

confidence: 99%

Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways

Zhou

Song

Liu

et al. 2015

IJMS

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Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an orally available form of berberine) on osteoclast differentiation and its underlying molecular mechanisms of action were investigated. Using bone marrow macrophages (BMMs) derived osteoclast culture system, we showed that berberine sulfate at the dose of 0.25, 0.5 and 1 μM significantly inhibited the formation of osteoclasts. Notably, berberine sulfate at these doses did not affect the BMM viability. In addition, we observed that berberine sulfate inhibited the expression of osteoclast marker genes, including cathepsin K (Ctsk), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP, Acp5) and Vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2). Luciferase reporter gene assay and Western blot analysis further revealed that berberine sulfate inhibits receptor for activation of nuclear factor ligand (RANKL)-induced NF-κB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis.

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“…Previous studies have shown that triptolide has an effect on CD4 + and CD8 + cells in Peyer's patch and might be associated with immunosuppressive activities [ 26 ]. Triptolide plays a pivotal role in the inhibition of bone resorption by acting on osteoclasts and decreasing their resorption [ 27 ]. Wang et al also revealed that triptolide can enhance the levels of IL-10 in CIA rats and decrease the expression of T cell receptor variable gene mRNA [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Triptolide Inhibits Osteoclast Differentiation and Bone ResorptionIn Vitrovia Enhancing the Production of IL-10 and TGF-β1 by Regulatory T Cells

Zhao

Lü

et al. 2016

Mediators of Inflammation

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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.

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Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-қB activation and titanium particle-induced osteolysis in a mouse model

Cited by 39 publications

References 31 publications

A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response

A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response

Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways

Triptolide Inhibits Osteoclast Differentiation and Bone ResorptionIn Vitrovia Enhancing the Production of IL-10 and TGF-β1 by Regulatory T Cells

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