Effect of Triptolide on T‐Cell Receptor Beta Variable Gene mRNA Expression in Rats With Collagen‐Induced Arthritis

Wang, Jixi; Wang, Aibing; Zeng, Hongyun; Liu, Lantao; Jiang, Wenhao; Zhu, Yongjie; Xu, You‐Ping

doi:10.1002/ar.22479

Cited by 23 publications

(14 citation statements)

References 27 publications

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“…However, the clinical use of these therapies has been limited because of their adverse effects with a high frequency and high cost of treatment. Extracts of the herb Tripterygium Wilfordii Hook f. (TWHF), also known as “Lei Gong Teng”, are clinically used as one of the most common systemic treatments for (auto) immune disorders including RA, immune complex nephritis, and systemic lupus erythematosus [11, 12]. It has been extensively used for centuries in China because of its favorable cost-benefit ratio.…”

Section: Introductionmentioning

confidence: 99%

Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

Liu

Zhang

Kong

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Focal bone destruction within inflamed joints is the most specific hallmark of rheumatoid arthritis (RA). Our previous study indicated that the therapeutic efficiency of triptolide in RA may be due partially to its chondroprotective and anti-inflammatory effects. However, its roles in bone destruction are still unclear. In this study, our data firstly showed the therapeutic effects of triptolide on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) mice. Then, by micro-CT quantification, triptolide treatment significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints. Interestingly, triptolide treatment could prevent the bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of NF-κB (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in sera and inflamed joints of CIA mice, which were further confirmed in the coculture system of human fibroblast-like synovial and peripheral blood mononuclear cells. These findings offer the convincing evidence for the first time that triptolide may attenuate RA partially by preventing the bone destruction and inhibit osteoclast formation by regulating RANKL/RANK/OPG signal pathway.

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Section: Introductionmentioning

confidence: 99%

Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

Liu

Zhang

Kong

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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“…Although these drugs are all clinically used to relieve the severity of RA, slow this disease progression, and prevent the subsequent joint damage [8]–[9], their clinical use has been limited because of their adverse effects with a high frequency and high cost of treatment. Extracts of the Chinese herb Tripterygium Wilfordii Hook f. (TWHF), also known as “Lei Gong Teng”, are clinically used as one of the most common systemic treatments for (auto) immune disorders including RA, immune complex nephritis and systemic lupus erythematosus [10]–[11]. It has been extensively used for centuries in China because of its favorable cost-benefit ratio.…”

Section: Introductionmentioning

confidence: 99%

Anti-Angiogenic Effect of Triptolide in Rheumatoid Arthritis by Targeting Angiogenic Cascade

et al. 2013

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Rheumatoid arthritis (RA) is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA) model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11–45 µg/kg/day) starting on the day 1 after first immunization. The arthritis scores (P<0.05) and the arthritis incidence (P<0.05) of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 11∼45 µg/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05). Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS–RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS–RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-β-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the angiogenic activators and inhibiting the activation of mitogen-activated protein kinase downstream signal pathway.

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“…The current researches on the mechanism of TPL in the treatment of RA mainly includes the following aspects: Wang et al () applied TPL to collagen‐induced RA mice, suggesting that TPL could improve arthritis symptoms of RA by inhibiting the secretion of inflammatory cytokines by T lymphocytes; Kong et al () proposed that TPL could inhibit the inflammation of RA by blocking the angiogenesis at the inflammatory site; Su, Sun, Ao, and Zhao () proposed that TPL could mediate the apoptosis of fibroblast‐like synoviocytes and inhibit their inflammation to improve the symptoms of RA. Fan et al () found that TPL could inhibit the degree of inflammation through TREM‐1 signaling pathway; Liu et al () proposed that TPL could block RANKL/RANK/OPG signaling pathways in collagen‐induced RA mice to prevent the formation of OCs from OCPs, thereby inhibiting bone destruction of RA.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Liu

Wang

et al. 2018

Phytotherapy Research

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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). TNFtransgenic 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.

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Effect of Triptolide on T‐Cell Receptor Beta Variable Gene mRNA Expression in Rats With Collagen‐Induced Arthritis

Cited by 23 publications

References 27 publications

Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

Anti-Angiogenic Effect of Triptolide in Rheumatoid Arthritis by Targeting Angiogenic Cascade

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

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