{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:37:57Z","timestamp":1792985877094,"version":"4.5.0"},"reference-count":428,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG KE 2179\/2-1"],"award-info":[{"award-number":["DFG KE 2179\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TS 303\/2"],"award-info":[{"award-number":["TS 303\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Else-Kr\u00f6ner-Fresenius Stiftung","award":["EKFS 2017_A22"],"award-info":[{"award-number":["EKFS 2017_A22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As brain and bone disorders represent major health issues worldwide, substantial clinical investigations demonstrated a bidirectional crosstalk on several levels, mechanistically linking both apparently unrelated organs. While multiple stress, mood and neurodegenerative brain disorders are associated with osteoporosis, rare genetic skeletal diseases display impaired brain development and function. Along with brain and bone pathologies, particularly trauma events highlight the strong interaction of both organs. This review summarizes clinical and experimental observations reported for the crosstalk of brain and bone, followed by a detailed overview of their molecular bases. While brain-derived molecules affecting bone include central regulators, transmitters of the sympathetic, parasympathetic and sensory nervous system, bone-derived mediators altering brain function are released from bone cells and the bone marrow. Although the main pathways of the brain-bone crosstalk remain \u2018efferent\u2019, signaling from brain to bone, this review emphasizes the emergence of bone as a crucial \u2018afferent\u2019 regulator of cerebral development, function and pathophysiology. Therefore, unraveling the physiological and pathological bases of brain-bone interactions revealed promising pharmacologic targets and novel treatment strategies promoting concurrent brain and bone recovery.<\/jats:p>","DOI":"10.3390\/ijms21144946","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"4946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Crosstalk of Brain and Bone\u2014Clinical Observations and Their Molecular Bases"],"prefix":"10.3390","volume":"21","author":[{"given":"Ellen","family":"Otto","sequence":"first","affiliation":[{"name":"Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul-Richard","family":"Knapstein","sequence":"additional","affiliation":[{"name":"Clinic of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Jahn","sequence":"additional","affiliation":[{"name":"Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessika","family":"Appelt","sequence":"additional","affiliation":[{"name":"Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Frosch","sequence":"additional","affiliation":[{"name":"Clinic of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-6864","authenticated-orcid":false,"given":"Serafeim","family":"Tsitsilonis","sequence":"additional","affiliation":[{"name":"Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-7288","authenticated-orcid":false,"given":"Johannes","family":"Keller","sequence":"additional","affiliation":[{"name":"Clinic of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s11154-015-9312-5","article-title":"Bone, brain & beyond","volume":"16","author":"Chamouni","year":"2015","journal-title":"Rev. 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