@Article{ecn.2019.0428,
AUTHOR = {Meiying Cui, Xin Li, Yimeng Lei, Liping Xia, Jing Lu, Hui Shen},
TITLE = {Effects of IL-34 on the secretion of RANKL/OPG by fibroblast-like synoviocytes and peripheral blood mononuclear cells in rheumatoid arthritis},
JOURNAL = {European Cytokine Network},
VOLUME = {30},
YEAR = {2019},
NUMBER = {2},
PAGES = {67--73},
URL = {http://www.techscience.com/ECN/v30n2/65396},
ISSN = {1952-4005},
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.},
DOI = {10.1684/ecn.2019.0428}
}