biomolecules Review Interactions between Muscle and Bone—Where Physics Meets Biology Marietta Herrmann 1 , Klaus Engelke 2 , Regina Ebert 3 , Sigrid Müller-Deubert 3 , Maximilian Rudert 4 , Fani Ziouti 5 , Franziska Jundt 5 , Dieter Felsenberg 6 and Franz Jakob 3,4, * 1 Orthopedic Department, Bernhard-Heine-Center for Locomotion Research, IZKF Research Group Tissue regeneration in musculoskeletal diseases, University Hospital Würzburg, University of Wuerzburg, 97070 Würzburg, Germany; m-herrmann.klh@uni-wuerzburg.de 2 Department of Medicine 3, FAU University Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054 Erlangen, Germany; klaus.engelke@imp.uni-erlangen.de 3 Orthopedic Department, Bernhard-Heine-Center for Locomotion Research, University of Würzburg, IGZ, 97076 Würzburg, Germany; r-ebert.klh@uni-wuerzburg.de (R.E.); s-mueller-deubert.klh@uni-wuerzburg.de (S.M-D.) 4 Orthopedic Department, Bernhard-Heine-Center for Locomotion Research, University of Würzburg, 97074 Würzburg, Germany; m-rudert.klh@uni-wuerzburg.de 5 Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany; Ziouti_F@ukw.de (F.Z.); Jundt_F@ukw.de (F.J.) 6 Privatpraxis für Muskel- und Knochenkrankheiten, 12163 Berlin Germany; dieter.felsenberg@charite.de * Correspondence: f-jakob.klh@uni-wuerzburg.de Received: 8 January 2020; Accepted: 5 March 2020; Published: 10 March 2020   Abstract: Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment. Keywords: muscle; bone; mechanosensing; mechanotransduction; myokines; osteokines adaptation 1. Introduction Bone and muscle are both tissues of mesodermal origin that together with joints constitute the musculoskeletal functional unit to facilitate the locomotion of the organism, which is guided by the central nervous system and the neuronal networks and their neuromuscular junctions. Both tissues provide a highly flexible system of adaptation as a response to the variability of physical forces generated Biomolecules 2020, 10, 432; doi:10.3390/biom10030432 www.mdpi.com/journal/biomolecules