Metformin repositioning in rheumatoid arthritis
Metformin repositioning in rheumatoid arthritis
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DOI：
10.55563/clinexprheumatol/zn2u9h
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发表时间：
2021-07-01
影响因子：
3.7
通讯作者：
Tamura, N.
中科院分区：
文献类型：
--
作者：
Matsuoka, Y.;Morimoto, S.;Tamura, N.
二甲双胍是已知的糖尿病治疗剂。最近，一些报告表明，通过二甲双胍对免疫系统的影响，有可能改善自身免疫性疾病和恶性肿瘤。尽管有关于二甲双胍对胶原诱导的关节炎小鼠模型（模拟人类风湿性关节炎（RA））的治疗作用的报告，但二甲双胍对人RA的作用仍未知。因此，我们研究了二甲双胍对体外人RA发病机制的抑制作用。MethodsOsteoclastogenesis与或不与二甲双胍进行了评价。通过抗酒石酸酸性磷酸酶染色、破骨细胞特异性酶表达分析和骨吸收测定。用TNF-α刺激人成纤维细胞样滑膜细胞MH 7A细胞，在有或没有二甲双胍的情况下评价促炎细胞因子和蛋白酶及生长因子基因的表达。已使用代谢物来评估其对用TNF-α处理的细胞的潜在调节作用。此外，我们检查血管生成进行管形成试验，使用人脐静脉内皮细胞（HUVECs）与或不与二甲双胍。ResultsOsteoclastogenesis抑制二甲双胍的存在下，和破骨细胞特异性基因的表达减少。二甲双胍可下调TNF-α诱导的MH 7A细胞中炎性细胞因子、蛋白酶和生长因子基因的表达。此外，诱导形成的HUVECs中的管状网络也被破坏后治疗与metformin.ConclusionThese结果表明，二甲双胍可能会改善RA的发病机制，包括关节炎症和破坏。因此，二甲双胍可能被用作治疗RA的潜在治疗剂。
ObjectiveMetformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autointmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro.MethodsOsteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-alpha, and the expression of proinflantmatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-alpha. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin.ResultsOsteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-alpha-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin.ConclusionThese results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.