title: IL-18 upregulates the production of key regulators of osteoclastogenesis from fibroblast-like synoviocytes in rheumatoid arthritis.
abstract: Recent data have demonstrated the importance of IL-18 in the induction and perpetuation of chronic inflammation in experimental arthritis. The aim of the present study was to elucidate whether IL-18 has any indirect effects on osteoclastogenesis by regulating the production of molecules from fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Human FLS were isolated from RA synovial tissue and cultured in vitro for three to five passages. The expression of IL-18 receptor was determined by RT-PCR. The levels of soluble receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in culture supernatants were determined by ELISA. Membrane-bound RANKL expression was analyzed by flow cytometry. Both α and β chains of IL-18 receptor were confirmed in cultured FLS. IL-18 upregulated membrane-bound RANKL expression and soluble RANKL production by FLS in both time- and dose-dependent manners. In addition, IL-18 enhanced production of M-CSF, GM-CSF, and OPG from cultured FLS in a dose-dependent manner. IL-18 also increased the ratio of RANKL/OPG, suggesting that the net effect of IL-18 on FLS favors for the induction of osteoclast formation and bone resorption. In conclusion, IL-18 upregulates the production of key regulators of osteoclastogenesis from FLS in RA.
authors.affiliation: Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Cong
authors.forename: Yang-Hua
authors.initials: YH
authors.lastname: Qin
authors.forename: Zheng-Wen
authors.initials: ZW
authors.lastname: He
authors.forename: Dong-Yi
authors.initials: DY
authors.lastname: He
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Dai
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D007249:Inflammation; D020382:Interleukin-18 / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit / Q000096:biosynthesis; D053728:Interleukin-18 Receptor beta Subunit / Q000096:biosynthesis; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D013583:Synovial Membrane / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor