{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:19:02Z","timestamp":1793215142658,"version":"4.5.0"},"reference-count":317,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272608"],"award-info":[{"award-number":["82272608"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11DZ2261100"],"award-info":[{"award-number":["11DZ2261100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Oriental Talent Program Youth","award":["82272608"],"award-info":[{"award-number":["82272608"]}]},{"name":"Shanghai Oriental Talent Program Youth","award":["11DZ2261100"],"award-info":[{"award-number":["11DZ2261100"]}]},{"name":"Shanghai Key Laboratory of Human Performance","award":["82272608"],"award-info":[{"award-number":["82272608"]}]},{"name":"Shanghai Key Laboratory of Human Performance","award":["11DZ2261100"],"award-info":[{"award-number":["11DZ2261100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>In recent years, the bidirectional regulatory mechanism of the bone-brain axis has become a hotspot for interdisciplinary research. In this paper, we systematically review the anatomical and functional links between bone and the central nervous system, focusing on the regulation of brain function by bone-derived signals and their clinical translational potential. At the anatomical level, the blood\u2013brain barrier permeability mechanism and the unique structure of the periventricular organs establish the anatomical basis for bone-brain information transmission. Innovative discoveries indicate that the bone cell network (bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone marrow monocytes) directly regulates neuroplasticity and the inflammatory microenvironment through the secretion of factors such as osteocalcin, lipid transporter protein 2, nuclear factor \u03baB receptor-activating factor ligand, and fibroblast growth factor 23, as well as exosome-mediated remote signaling. Clinical studies have revealed a bidirectional vicious cycle between osteoporosis and Alzheimer\u2019s disease: reduced bone density exacerbates Alzheimer\u2019s disease pathology through pathways such as PDGF-BB, while AD-related neurodegeneration further accelerates bone loss. The breakthrough lies in the discovery that anti-osteoporotic drugs, such as bisphosphonates, improve cognitive function. In contrast, neuroactive drugs modulate bone metabolism, providing new strategies for the treatment of comorbid conditions. Additionally, whole-body vibration therapy shows potential for non-pharmacological interventions by modulating bone-brain interactions through the mechano-osteoclast signaling axis. In the future, it will be essential to integrate multiple groups of biomarkers to develop early diagnostic tools that promote precise prevention and treatment of bone-brain comorbidities. This article provides a new perspective on the mechanisms and therapeutic strategies of neuroskeletal comorbidities.<\/jats:p>","DOI":"10.3390\/biology14091112","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:31:26Z","timestamp":1755865886000},"page":"1112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bone-Derived Factors: Regulating Brain and Treating Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Qiao","family":"Guan","sequence":"first","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","first-page":"309","article-title":"Bone Marrow-Derived Myeloid Cells Drive Neuroinflammation in Alzheimer\u2019s Disease: Insights from the FAD(4T) Mouse Model","volume":"53","author":"Pang","year":"2025","journal-title":"J. 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