SAT0031 Interleukin 29 inhibits osteoclast differentiation and function in rankl-induced osteoclastogenesis
Authors: F. Wang, A. Luo, Q. Wu, Z. Zhou, Q. Peng, W. Xuan, W. Tan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interleukin-29 (IL-29) is a new member of the recently discovered interferon (IFN) λ family and known to modulate immune functions of monocyte or macrophage. We have demonstrated that IL-29 is dysregulated in patients with rheumatoid arthritis (RA) and contributes to RA pathogenesis via inducing proinflammatory cytokines, chemokines or matrix metalloproteinases production in synovial fibroblasts,<sup>1, 2</sup> as well as stimulating inflammation and cartilage degradation in osteoarthritis disease.<sup>3</sup> However, the role of IL-29 in bone resorption is unclear. <h3>Objectives</h3> Bone erosion in RA is associated with increased production of pro-inflammatory cytokines and accelerated osteoclastogenesis in affected joints.<sup>4</sup> IL-29 is an important proinflammatory cytokine in RA. We investigated the effect of IL-29 on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis <i>in vitro</i> to determine whether IL-29 can stimulate or attenuate osteoclast-mediated bone resorption that is a hallmark of RA. <h3>Methods</h3> The viability and apoptosis of RAW264.7 cells after IL-29 different treatment were assessed by Cell Counting Kit-8 and flow cytometry, respectively.Osteoclasts were generated from RAW264.7 cells, bone-marrow-derived monocyte/macrophage precursor cells (BMMs) and blood-derived human PBMC cells. The effects of IL-29 on osteoclast formation were evaluated by tartrate-resistant acid phosphatase (TRAP) staining and counting the number of TRAP +multinucleated cells. Bone resorption experiment was assessed by pit formation. The expression of key molecules implicated in osteoclastogenesis (TRAP, CTSK, MMP-9, NFATC1 and c-Fos) was measured by real time RT-PCR. <h3>Results</h3> Although IL-29 did not show significant effect on the viability and apoptosis of RAW264.7 cells, it inhibited multinucleated cells in the differentiation of murine and human osteoclastogenesis, the bone-resorbing activity of mature osteoclasts. In addition, IL-29 downregulated osteoclastic specific genes expression of TRAP, CTSK, MMP-9, NFATC1 and c-Fos. <h3>Conclusions</h3> IL-29 inhibits murine and human osteoclastogenesis by a direct mechanism suppressing responses of osteoclast precursors to RANKL. Our findings suggest that IL-29 may play a previously unrecognised role in the osteoclast formation. <h3>References</h3> [1] Wang F, Xu L, Feng X, Guo D, Tan W, Zhang M. Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis. Arthritis Res Ther2012;14;R228. [2] Xu L, Feng X, Tan W, Gu W, Guo D, Zhang M, Wang F. IL-29 enhances Toll-like receptor-mediated IL-6 and IL-8 production by the synovial fibroblasts from rheumatoid arthritis patients. Arthritis Res Ther2013;15:R170. [3] Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F. Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis. Mediators Inflamm2016;2016:9631510. [4] Schett G, Gravallese E. Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol2012;8:656–664. <h3>Acknowledgements</h3> This project was sponsored by the grants from the National Natural Science Foundation of China (No. 81671610, 81471610, 81471611, 81401352, 81172845, 81671615, and bk20141021). <h3>Disclosure of Interest</h3> None declared