{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:01:31Z","timestamp":1784818891750,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300992"],"award-info":[{"award-number":["82300992"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Beyond established roles in metabolic regulation, adipose tissue\u2010derived factors are increasingly recognized as critical modulators of bone mass. Nevertheless, the underlying mechanisms that coordinate the osteoclastogenesis\u2013angiogenesis\u2013osteogenesis axis to maintain skeletal homeostasis remain poorly defined. Mouse models including brown adipose tissue (BAT) removal, Neuregulin 4 (Nrg4) knockout (\n                    <jats:italic>Nrg4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ), and BAT transplantation were used to evaluate the role of BAT\u2010secreted Nrg4 in bone homeostasis. In\u00a0vitro experiments were performed to explore the effects of Nrg4 on osteoclastogenesis and the angiogenesis\u2013osteogenesis coupling. Additionally, exogenous Nrg4 treatment was applied to ovariectomy (OVX)\u2010induced osteoporotic mice to assess its therapeutic potential. BAT removal or Nrg4 knockout resulted in increased bone resorption and decreased bone formation, thereby accelerating bone loss in mice; conversely, BAT transplantation rescued the skeletal phenotype of\n                    <jats:italic>Nrg4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. In\u00a0vitro, Nrg4 significantly inhibited osteoclastogenesis, at least partially through the NF\u2010\u03baB inflammatory signaling pathway, while simultaneously activating the angiogenesis\u2013osteogenesis coupling via PDGF\u2010BB derived from preosteoclasts. Furthermore, exogenous Nrg4 treatment effectively attenuated bone loss in OVX\u2010induced osteoporotic mice. These findings demonstrate that BAT\u2010derived Nrg4 acts as a key regulator of bone homeostasis and represents a promising therapeutic target for bone loss disorders by orchestrating crosstalk between osteoclasts and endothelial cells.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601258rr","type":"journal-article","created":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T17:15:29Z","timestamp":1783271729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brown Adipose Tissue Secreted Nrg4 Prevents Bone Loss by Orchestrates Bone Resorption and Angiogenesis"],"prefix":"10.1096","volume":"40","author":[{"given":"Xiaoli","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital (Southwest Hospital) of Army Medical University  Chongqing People's Republic of China"},{"name":"Key Laboratory of Infection and Immunity, Health Commission of Jiangxi Province &amp; School of Basic Medicine Nanchang Medical College  Nanchang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianrong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjia","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital (Southwest Hospital) of Army Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First Affiliated Hospital (Southwest Hospital) of Army Medical University  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