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Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany
Clinic of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(14), 4946;
Received: 17 June 2020 / Revised: 6 July 2020 / Accepted: 6 July 2020 / Published: 13 July 2020
(This article belongs to the Special Issue Biological Basis of Musculoskeletal Regeneration 2019)
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 ‘efferent’, signaling from brain to bone, this review emphasizes the emergence of bone as a crucial ‘afferent’ 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. View Full-Text
Keywords: brain; bone; interaction; clinical and experimental studies; molecular signaling brain; bone; interaction; clinical and experimental studies; molecular signaling
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MDPI and ACS Style

Otto, E.; Knapstein, P.-R.; Jahn, D.; Appelt, J.; Frosch, K.-H.; Tsitsilonis, S.; Keller, J. Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases. Int. J. Mol. Sci. 2020, 21, 4946.

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