Open Access

ORIGINAL ARTICLE

Effects of IL-34 on the secretion of RANKL/OPG by fibroblast-like synoviocytes and peripheral blood mononuclear cells in rheumatoid arthritis

Meiying Cui¹, Xin Li^1,2, Yimeng Lei¹, Liping Xia¹, Jing Lu¹, Hui Shen¹

1 1st Affiliated Hospital of China Medical University, Department of Rheumatology, Shen Yang, 110001, China
2 Department of Rheumatology, 1st Affiliated Hospital of Jinzhou Medical University, Jin Zhou, China, 121000

* Corresponding Author: Hui Shen,

European Cytokine Network 2019, 30(2), 67-73. https://doi.org/10.1684/ecn.2019.0428

Accepted 09 April 2019;

Abstract

Objective: To detect the effect of interleukin (IL)-34 on the secretion of Receptor activator of nuclear factor kappa-B ligand (RANKL)/Osteoprotegerin (OPG) and Matrix metalloproteinase (MMP)-3 by fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and to investigate whether the effect is mediated by IL-17. Method: RA-FLS and RA-PBMCs were stimulated with recombinant human (rh) IL-34, with or without the IL-17 inhibitor Plumbagin. The supernatant of the culture medium was collected and the levels of RANKL, OPG, and MMP-3 were detected by enzyme-linked immunosorbent assay (ELISA). Results: RhIL-34 promoted RANKL secretion and inhibited OPG secretion in RA-FLS. The effect was weakened by the addition of the IL-17 inhibitor. In contrast, rhIL-34 had no significant effect on MMP-3 secretion by FLS. RhIL-34 elevated the secretion of RANKL by RA-PBMCs but not by healthy-PBMCs. Furthermore, the secretion of RANKL by RA-PBMCs reduced after the addition of the IL-17 inhibitor. OPG secretion by both RA-FLS and FLS from healthy controls was inhibited by rhIL-34, but were elevated after the addition of the IL-17 inhibitor. RhIL-34 had no significant effect on MMP-3 secretion by both RA-PBMCs and healthy-PBMCs. Conclusion: IL-34 enhances RANKL/OPG expression by RA-FLS and RA-PBMCs, and this effect is, indirectly, mediated by IL-17. This cytokine is therefore likely to to play an important role in local joint destruction and systemic osteoporosis in RA, and is therefore a potential therapeutic target for the treatment of this disease.

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