{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:23:23Z","timestamp":1777451003669,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The homeostatic balance of bone remodeling is governed by the precise coordination between bone\u2010forming osteoblasts and bone\u2010resorbing osteoclasts. In this study, we investigated the anti\u2010resorptive properties of rhamnocitrin\u20103\u2010rhamnoside (Rh3R), a flavonoid isolated from\n                    <jats:italic>Loranthus tanakae<\/jats:italic>\n                    , using primary bone marrow\u2010derived macrophages (BMMs) and calvaria\u2010derived osteogenic progenitor cells (COCs) to ensure biological relevance. Our findings demonstrate that Rh3R potently inhibits the RANKL\u2010induced differentiation of BMMs into TRAP\u2010positive multinucleated osteoclasts in a dose\u2010dependent manner, without inducing cytotoxicity. Mechanistically, Rh3R effectively attenuates RANKL\u2010induced downstream signaling cascades, as evidenced by the attenuated phosphorylation of MAPKs (ERK1\/2, JNK, p38), AKT, and I\u03baB. This signaling blockade subsequently suppresses the induction of the master transcription factors, c\u2010Fos and NFATc1. Furthermore, Rh3R impairs the functional resorptive capacity of mature osteoclasts by destabilizing F\u2010actin\u2010rich ring structures accompanied by decreased integrin \u03b23 expression, thereby preventing the formation of a functional sealing zone. The inhibitory effect of Rh3R on bone\u2010degrading activity was further confirmed by a significant reduction in the total area of resorption pits on bone slices. Notably, Rh3R exhibits a lineage\u2010specific inhibitory effect, showing no adverse influence on osteoblastogenesis or the mineralizing capacity of primary osteogenic cells. Furthermore, the effect of Rh3R was consistently maintained in a co\u2010culture system of primary osteoblasts and BMMs. Collectively, these\n                    <jats:italic>in vitro<\/jats:italic>\n                    findings identify Rh3R as a bioactive modulator of osteoclast differentiation and function via suppression of RANKL\u2010induced downstream signaling, warranting future\n                    <jats:italic>in vivo<\/jats:italic>\n                    and pharmacological studies to evaluate efficacy, exposure, and safety.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70174","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:25:02Z","timestamp":1776320702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rh3R Attenuates RANKL\u2010Induced Osteoclast Differentiation and F\u2010Actin Ring Formation via the Suppression of c\u2010Fos\/NFATc1 Signaling in Primary Murine Cells"],"prefix":"10.1002","volume":"241","author":[{"given":"Hyung\u2010Mun","family":"Yun","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology School of Dentistry Kyung Hee University Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"National Institute for Korean Medicine Development Gyeongsan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joonyeop","family":"Lee","sequence":"additional","affiliation":[{"name":"National Institute for Korean Medicine Development Gyeongsan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010Ran","family":"Park","sequence":"additional","affiliation":[{"name":"Honam Regional Center Korea Basic Science Institute Gwangju Republic of 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