title: Mechanically loaded myotubes affect osteoclast formation.
abstract: In response to mechanical loading skeletal muscle produces numerous growth factors and cytokines that enter the circulation. We hypothesized that myotubes produce soluble factors that affect osteoclast formation and aimed to identify which osteoclastogenesis-modulating factors are differentially produced by mechanically stimulated myotubes. C2C12 myotubes were subjected to mechanical loading by cyclic strain for 1 h, and postincubated with or without cyclic strain for 24 h. The effect of cyclic strain on gene expression in myotubes was determined by PCR. Conditioned medium (CM) was collected from cultures of unloaded and loaded myotubes and from MLO-Y4 osteocytes. CM was added to mouse bone marrow cells containing osteoclast precursors, and after 6 days osteoclasts were counted. Compared to unconditioned medium, CM from unloaded osteocytes increased osteoclast formation, while CM from unloaded myotubes decreased osteoclast formation. Cyclic strain strongly enhanced IL-6 expression in myotubes. CM from cyclically strained myotubes increased osteoclast formation compared to CM from unloaded myotubes, but this effect did not occur in the presence of an IL-6 antibody. In conclusion, mechanically loaded myotubes secrete soluble factors, among others IL-6, which affect osteoclast formation. These results suggest that muscle could potentially affect bone homeostasis in vivo via production of growth factors and/or cytokines.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, 1081 LA, Amsterdam, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Juffer
authors.forename: Richard T
authors.initials: RT
authors.lastname: Jaspers
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Bakker
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D015850:Interleukin-6; D053245:RANK Ligand