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Adv."],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:p>\n                    Chronic stress disrupts skeletal homeostasis, yet central neural mechanisms remain unclear. In this study, we demonstrated that hyperactivation of locus coeruleus noradrenergic (LC\n                    <jats:sup>NE+<\/jats:sup>\n                    ) neurons was both necessary and sufficient to drive bone loss in a mouse model of chronic social defeat stress (CSDS). Mechanistically, CSDS induced a bidirectional imbalance in the central amygdala corticotropin-releasing hormone (CRH)\u2013expressing (CeA\n                    <jats:sup>CRH+<\/jats:sup>\n                    ) neurons to LC\n                    <jats:sup>NE+<\/jats:sup>\n                    circuit, characterized by enhanced CRH release and suppressed GABAergic transmission. A CeA\n                    <jats:sup>CRH+<\/jats:sup>\n                    -LC\n                    <jats:sup>NE+<\/jats:sup>\n                    -paraventricular hypothalamic CRH\u2013expressing (PVH\n                    <jats:sup>CRH+<\/jats:sup>\n                    ) pathway was identified, which propagated stress signals to bone via sympathetic outflows. These findings redefine central bone metabolism control by establishing LC\n                    <jats:sup>NE+<\/jats:sup>\n                    neurons as key stress-responsive hubs. Restoration of CRH\/\u03b3-aminobutyric acid balance within the CeA\n                    <jats:sup>CRH+<\/jats:sup>\n                    -LC\n                    <jats:sup>NE+<\/jats:sup>\n                    circuit reversed CSDS-induced bone loss. Targeted inhibition of the CeA\n                    <jats:sup>CRH+<\/jats:sup>\n                    -LC\n                    <jats:sup>NE+<\/jats:sup>\n                    -PVH\n                    <jats:sup>CRH+<\/jats:sup>\n                    pathway effectively mitigated stress-related osteoporosis, suggesting neural pathway\u2013directed interventions as a promising therapeutic strategy for stress-induced bone pathology.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz9329","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T18:58:31Z","timestamp":1764961111000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["A central CeA-LC-PVH circuit mediates stress-induced osteopenia via skeletal sympathetic nerves in male mice"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1255-4182","authenticated-orcid":true,"given":"Wen-Jun","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."},{"name":"Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi\u2019an 710032, China."},{"name":"Medical Centre for Neck and Low Back Pain, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8079-4715","authenticated-orcid":true,"given":"Yu-Xin","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Di","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."},{"name":"College of Life Science, Northwest University, Xi\u2019an 710069, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5333-3989","authenticated-orcid":true,"given":"Chao-Yang","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Pei","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0789-7606","authenticated-orcid":true,"given":"Bin","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."},{"name":"Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang-Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi\u2019an 710032, China."},{"name":"Xi\u2019an Medical College, Xi\u2019an 710021, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1162-3986","authenticated-orcid":true,"given":"Chu-Han","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, K. K. 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