{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:27:44Z","timestamp":1781566064045,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoporosis (OP) is a chronic skeletal disorder characterized by reduced bone mineral density and increased fracture risk, particularly from hip fractures linked to a 20%\u201324% increased mortality risk within the first year. Current therapies remained inadequate in addressing metabolic drivers, which prompted exploration of novel targets. Fabkin, a recently identified hormonal complex comprising fatty acid\u2010binding protein 4 (FABP4), nucleoside diphosphate kinase (NDPK), and adenosine kinase (ADK), was implicated in metabolic and inflammatory signaling. It was suggested that Fabkin could promote Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx and the release of inflammatory factors via the PKA pathway. However, its role in bone loss remained unclear. To investigate the role of Fabkin in OP, an ovariectomy (OVX)\u2010induced murine model was used to simulate estrogen\u2010deficient osteoporosis. FABP4\u2010KO mice were generated to disrupt Fabkin formation, and bone microarchitecture was assessed using micro\u2010CT and histological staining. Osteoclastogenesis assays in\u00a0vitro were conducted using bone marrow\u2010derived macrophages (BMDMs) treated with recombinant Fabkin components. Western blotting and RT\u2010qPCR were performed to analyze key signaling pathways involved in osteoclast differentiation, particularly MAPK and NF\u2010\u03baB. Immunofluorescence analysis revealed an increase in Fabkin expression in the bone marrow of OVX mice. OVX\u2010induced osteoporosis was significantly attenuated in FABP4\u2010KO mice with higher BMD. TRAP staining showed a reduction in osteoclast numbers in FABP4\u2010KO mice. In\u00a0vitro, Fabkin treatment significantly enhanced osteoclast differentiation and bone resorption, whereas FABP4 deficiency inhibited osteoclast formation. Molecular analysis revealed that Fabkin promoted osteoclastogenesis via the RANKL\u2010induced MAPK and NF\u2010\u03baB signaling pathways. These findings suggested that FABP4 might directly exacerbate osteoclastogenesis by acting as a Fabkin complex instead of a lipid regulator.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501946r","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T15:32:57Z","timestamp":1758209577000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fabkin Promoted Osteoclasts Mature and Bone Loss in\n                    <scp>OVX<\/scp>\n                    \u2010Induced Osteoporosis Mice"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2231-3393","authenticated-orcid":false,"given":"Chenhao","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Sun Yat\u2010Sen Memorial Hospital Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Department of Orthopaedics &amp; Traumatology The University of Hong Kong  Hong Kong SAR 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