{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:17:26Z","timestamp":1792808246956,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bone Res"],"abstract":"<jats:title>\n                    <jats:bold>Abstract<\/jats:bold>\n                  <\/jats:title>\n                  <jats:p>\n                    DNAX-associated protein 12\u2009kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis. Although several DAP12-associated receptors (DARs) have been identified in osteoclasts, including triggering receptor expressed on myeloid cells 2 (TREM-2), C-type lectin member 5\u2009A (CLEC5A), and sialic acid-binding Ig-like lectin (Siglec)-15, their precise role in the development of osteoclasts and bone remodeling remain poorly understood. In this study, mice deficient in\n                    <jats:italic>Trem-2<\/jats:italic>\n                    ,\n                    <jats:italic>Clec5a<\/jats:italic>\n                    ,\n                    <jats:italic>Siglec-15<\/jats:italic>\n                    were generated. In addition, mice double deficient in these DAR genes and Fc\u03b5RI gamma chain (FcR)\u03b3, an alternative ITAM adaptor to DAP12, were generated. Bone mass analysis was conducted on all mice. Notably,\n                    <jats:italic>Siglec-15<\/jats:italic>\n                    deficient mice and\n                    <jats:italic>Siglec-15\/FcR\u03b3<\/jats:italic>\n                    double deficient mice exhibited mild and severe osteopetrosis respectively. In contrast, other DAR deficient mice showed normal bone phenotype. Likewise, osteoclasts from\n                    <jats:italic>Siglec-<\/jats:italic>\n                    15 deficient mice failed to form an actin ring, suggesting that Siglec-15 promotes bone resorption principally by modulating the cytoskeletal organization of osteoclasts. Furthermore, biochemical analysis revealed that Sigelc-15 activates macrophage colony-stimulating factor (M-CSF)-induced Ras-associated protein-1 (RAP1)\/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway through formation of a complex with p130CAS and CrkII, leading to cytoskeletal remodeling of osteoclasts. Our data provide genetic and biochemical evidence that Siglec-15 facilitates M-CSF-induced cytoskeletal remodeling of the osteoclasts.\n                  <\/jats:p>","DOI":"10.1038\/s41413-024-00340-w","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T07:05:48Z","timestamp":1717743948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Involvement of Siglec-15 in regulating RAP1\/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor"],"prefix":"10.1038","volume":"12","author":[{"given":"Hideyuki","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5481-8516","authenticated-orcid":false,"given":"M. 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Approval was granted by the Ethics Committee of Hokkaido University (# 20-0062).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}],"article-number":"35"}}