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| Effect of matrine on RANKL-induced osteoclast differentiation and the expression of TRAF6, c-fos and NFATc1 |
| LI Xin1 LI Fang2 WANG Yuan1 ZHANG Baoyu1 ZHANG Lijie1 |
1.Endocrine Metabolism and Immune Center, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China;
2.Department of Rheumatology, the Second Hospital of Shanxi Medical University, Shanxi Province, Taiyuan 030001, China |
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Abstract Objective To investigate the effect of matrine on RANKL-induced osteoclast differentiation and the possible molecular mechanism. Methods RAW264.7 cells were cultured. According to the different addition of drugs (none, osteoclast inducer RANKL and different doses of matrine), they were divided into blank group, induction group, low-dose matrine group (0.5 mg/mL), medium-dose matrine group (1 mg/mL) and high-dose matrine group (2 mg/mL). The expression of TRAF6, c-fos, NFATc1 mRNA and protein were detected by qPCR and Western blot at the 48th hour after administration. Multinucleated osteoclasts were observed by TRAP on the 7th day. The expression of Calcr and Ctsk mRNA was detected by qPCR on the 9th day. The bone resorption lacunae were observed by toluidine blue staining on the 12th day. Results Compared with induction group, the expression of osteoclasts, bone resorption lacuna, Calcr mRNA and Ctsk mRNA decreased in different dosage matrine group. The expression of TRAF6, c-fos and NFATc1 mRNA in different dosage groups of matrine was significantly lower than that in induction group (P < 0.01), and was dose-dependent. There was no significant difference in the expression of TRAF6, c-fos and NFATc1 mRNA between blank group and high dose group of matrine (P > 0.05). Compared with induction group, the expression of TRAF6, c-fos and NFATc1 protein in matrine low, middle and high dose groups decreased (P < 0.05), and it was dose-dependent. There was no significant difference in the expression of TRAF6, c-fos and NFATc1 between blank group and high dose group of matrine (P > 0.05). Conclusion Matrine may affect RANKL-induced osteoclasts differentiation by inhibiting the expression of TRAF6, c-fos and NFATc1.
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[1] Tanaka Y，Nakayamada S，Okada Y. Osteoblasts and osteoclasts in bone remodeling and inflammation [J]. Curr Drug Targets Inflamm Allergy，2005，4（3）：325-328.
[2] Tanaka S，Tanaka Y，Ishiguro N，et al. RANKL：a therapeutic target for bone destruction in rheumatoid arthritis [J]. Mod Rheumatol，2018，28（1）：9-16.
[3] Kaneko S，Kondo Y，Yokosawa M，et al. Rheumatoid arthritis and cytokines [J]. Nihon Rinsho，2016，74（6）：913-918.
[4] Park JH，Lee NK，Lee SY. Current understanding of RANK signaling in osteoclast differentiation and maturation [J]. Mol Cells，2017，40（10）：706-713.
[5] Takayanagi H. Mechanistic insight into osteoclast differentiation in osteoimmunology [J]. J Mol Med（Berl），2005，83（3）：170-179.
[6] Zhang L，Zhang H，Zhu Z，et al. Matrine regulates immune functions to inhibit the proliferation of leukemic cells [J]. Int J Clin Exp Med，2015，8（4）：5591-5600.
[7] Tateiwa D，Yoshikawa H，Kaito T. Cartilage and bone destruction in arthritis：pathogenesis and treatment strategy：a literature review [J]. Cells，2019，8（8）：E818.
[8] Tanaka S. RANKL is a therapeutic target of bone destruction in rheumatoid arthritis [J]. F1000Res，2019，8：F1000 Faculty Rev-533.
[9] Metzger CE，Narayanan SA. The role of osteocytes in inflammatory bone loss [J]. Front Endocrinol（Lausanne），2019，10：285.
[10] van Loo G，Beyaert R. Negative regulation of NF-κB and its involvement in rheumatoid arthritis [J]. Arthritis Res Ther，2011，13（3）：221.
[11] He X，Fang J，Huang L，et al. Sophora flavescens ait：traditional usage，phytochemistry and pharmacology of an important traditional Chinese medicine [J]. J Ethnopharmacol，2015，172：10-29.
[12] Qiu S，Sun H，Zhang AH，et al. Natural alkaloids：basic aspects，biological roles，and future perspectives [J]. Chin J Nat Med，2014，12（6）：401-406.
[13] Sun D，Wang J，Yang N，et al. Matrine suppresses airway inflammation by downregulating SOCS3 expression via inhibition of NF-κB signaling in airway epithelial cells and asthmatic mice [J]. Biochem Biophys Res Commun，2016，477（1）：83-90.
[14] Pu J，Fang FF，Li XQ，et al. Matrine exerts a strong anti-arthritic effect on type Ⅱ collagen-induced arthritis in rats by inhibiting inflammatory responses [J]. Int J Mol Sci，2016，17（9）：1410.
[15] Zou Y，Li Q，Liu D，et al. Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes [J]. Sci Rep，2017，7（1）：2454.
[16] Liu J，Liu Y，Li B，et al. Sophoridine suppresses inflammatory cytokine secretion by lipopolysaccharide-induced RAW264.7 cells and its mechanism [J]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi，2015，31（5）：585-589，595.
[17] Chen X，Zhi X，Pan P，et al. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis [J]. FASEB J，2017，31（11）：4855-4865.
[18] Niu Y，Dong Q，Li R. Matrine regulates Th1/Th2 cytokine responses in rheumatoid arthritis by attenuating the NF-κB signaling [J]. Cell Biol Int，2017，41（6）：611-621.
[19] Chen X，Zhi X，Cao L，et al. Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis [J]. Cell Death Dis，2017，8（9）：e3037.
[20] Xin Z，Jin C，Chao L，et al. A matrine derivative M54 suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by targeting ribosomal protein S5 [J]. Front Pharmacol，2018，9：22. |
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