@ARTICLE{10.3389/fimmu.2017.01376, AUTHOR={Kim, Jin-Hee and Sim, Ji Hyun and Lee, Sunkyung and Seol, Min A. and Ye, Sang-Kyu and Shin, Hyun Mu and Lee, Eun Bong and Lee, Yun Jong and Choi, Yun Jung and Yoo, Wan-Hee and Kim, Jin Hyun and Kim, Wan-Uk and Lee, Dong-Sup and Kim, Jin-Hong and Kang, Insoo and Kang, Seong Wook and Kim, Hang-Rae}, TITLE={Interleukin-7 Induces Osteoclast Formation via STAT5, Independent of Receptor Activator of NF-kappaB Ligand}, JOURNAL={Frontiers in Immunology}, VOLUME={8}, YEAR={2017}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2017.01376}, DOI={10.3389/fimmu.2017.01376}, ISSN={1664-3224}, ABSTRACT={Interleukin-7 (IL-7), which is required for the development and survival of T cells in the thymus and periphery, plays a role in joint destruction. However, it remains unclear how IL-7 affects osteoclast formation. Thus, we investigated the mechanism by which IL-7 induced osteoclast formation through IL-7 receptor α (IL-7Rα) in osteoclast precursors. We cultured peripheral blood mononuclear cells or synovial fluid mononuclear cells with IL-7 in the presence or absence of an appropriate inhibitor to analyze osteoclast formation. We also constructed IL-7Rα-expressing RAW264.7 cells to uncover the mechanism(s) by which IL-7 induced osteoclast formation differed from that of receptor activator of nuclear factor κB ligand (RANKL). We found that IL-7 induced osteoclast formation of human monocytes from peripheral blood or synovial fluid in a RANKL-independent and a signal transducer and activator of transcription 5 (STAT5)-dependent manner. IL-7-induced osteoclasts had unique characteristics, such as small, multinucleated tartrate-resistant acid phosphatase positive cells and no alterations even when RANKL was added after IL-7 pretreatment. RAW264.7 cells, if overexpressing IL-7Rα, also were able to differentiate into osteoclasts by IL-7 through a STAT5 signaling pathway. Furthermore, IL-7-induced osteoclast formation was repressed by inhibitors of the IL-7R signaling molecules Janus kinase and STAT5. Our findings demonstrate that IL-7 is a truly osteoclastogenic factor, which may induce osteoclast formation via activation of STAT5, independent of RANKL. We also suggest the possibility that an IL-7R pathway blocker could alleviate joint damage by inhibiting osteoclast formation, especially in inflammatory conditions.} }