Publication Date:
2016-09-09
Description:
Interleukin-15 (IL-15), a cytokine secreted by several cell types, has important physiological roles in the activity, proliferation, and viability of immune cells.It has both chemoattractant and proinflammatory properties, and may promote bone destruction. Aprevious study has shown that IL-15alone exertsno effect on osteoclastogenesis. Therefore,thecurrent study addressed the synergistic effect of IL-15 on osteoclast formation using RAW264.7(RAW) cellsby co-stimulation with receptor activator of nuclear factor (NF)-κB ligand (RANKL)that has a majorrole inosteoclastogenesis involving the pathogenesis of rheumatoid arthritis and periodontal disease.Co-stimulation of RAW cells by IL-15 and RANKL significantly increasedthe gene expression of osteoclast differentiation and osteoclastogenesismarkers comparedwith stimulation by RANKL or IL-15 independentlyas evaluated by tartrate-resistant acid phosphate-positive cell numbers, the fusion index, a pit formation assay with Alizarin redstaining (calcification estimation), and quantitative polymerase chain reaction. Phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, p38 mitogen-activated proteinkinase, and NF-κB wassignificantly increased by RANKL and IL-15 ( p 〈 0.05) compared with RANKL alone.In addition, thesedifferentiation activities induced by RANKL and IL-15were comparatively suppressed by inhibition of ERK, suggesting that this synergistic effect on osteoclastogenesis is mainlymediated by ERK. Taken together, our results demonstrate that IL-15 and RANKL induce osteoclastogenesis synergistically, and IL-15mightplaya novel and majorrole indestructiveinflammatory bone diseases. This article is protected by copyright. All rights reserved
Electronic ISSN:
0091-7419
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
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