{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:34:20Z","timestamp":1793255660840,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Calprotectin, a heterodimer of S100A8 and S100A9, is predominantly expressed in neutrophils, monocytes, and chondrocytes. Clinical studies demonstrate that elevated circulating calprotectin levels correlate with diseases followed by inflammatory bone loss, including rheumatoid arthritis, osteoarthritis, and periodontitis. We previously reported that S100A9 directly increased RANKL and IL\u20106 expression in an osteocyte\u2010like cell line. While RANKL is well\u2010established as an essential factor for the formation and activation of osteoclasts, the role of S100A9\u2010induced IL\u20106 in bone resorption remains unclear. On the other hand, osteocytes require sIL\u20106R to activate the gp130 signaling pathway. Therefore, we hypothesized that S100A9\u2010induced IL\u20106 cooperates with soluble IL\u20106 receptor (sIL\u20106R) to increase RANKL through gp130\u2010mediated signaling. Here, we show that S100A9 increases the bone resorption area and TRAP\u2010positive cell number in the murine calvaria. In addition,\n                    <jats:italic>Rankl<\/jats:italic>\n                    and\n                    <jats:italic>Il6<\/jats:italic>\n                    mRNA levels in osteocytes were upregulated by S100A9 treatment. In\u00a0vitro results demonstrated that S100A9 increased not only\n                    <jats:italic>Rankl<\/jats:italic>\n                    and\n                    <jats:italic>Il6<\/jats:italic>\n                    expression in osteocytes, but also sIL\u20106R secretion in macrophages. Since osteocytes strongly express gp130, the IL\u20106 complexed with sIL\u20106R enhanced gp130 downstream signaling, including JAK1 and STAT3 activation in osteocytes. Blockade of either\n                    <jats:italic>Il6<\/jats:italic>\n                    or gp130 suppressed S100A\u2010induced effects. Notably, gp130 antagonist treatment inhibited S100A9\u2010induced bone resorption in\u00a0vivo. Collectively, these findings suggest that S100A9 promotes RANKL\u2010mediated osteoclastogenesis through IL\u20106\/sIL\u20106\/gp130 signaling in osteocytes.\n                  <\/jats:p>","DOI":"10.1096\/fj.202603197r","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:07:06Z","timestamp":1791961626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>S100A9<\/scp>\n                    Induces\n                    <scp>RANKL<\/scp>\n                    Expression in Osteocytes Utilizing\n                    <scp>IL<\/scp>\n                    \u20106\/\n                    <scp>sIL<\/scp>\n                    \u2010\n                    <scp>6R<\/scp>\n                    Combination and gp130 Signaling 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