title: Skeletal muscle Ca(2+) mishandling: Another effect of bone-to-muscle signaling.
abstract: Our appreciation of crosstalk between muscle and bone has recently expanded beyond mechanical force-driven events to encompass a variety of signaling factors originating in one tissue and communicating to the other. While the recent identification of new 'myokines' has shifted some focus to the role of muscle in this partnership, bone-derived factors and their effects on skeletal muscle should not be overlooked. This review summarizes some previously known mediators of bone-to-muscle signaling and also recent work identifying a new role for bone-derived TGF-β as a cause of skeletal muscle weakness in the setting of cancer-induced bone destruction. Oxidation of the ryanodine receptor/calcium release channel (RyR1) in skeletal muscle occurs via a TGF-β-Nox4-RyR1 axis and leads to calcium mishandling and decreased muscle function. Multiple points of potential therapeutic intervention were identified, from preventing the bone destruction to stabilizing the RYR1 calcium channel. This new data reinforces the concept that bone can be an important source of signaling factors in pathphysiological settings.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Jenna N
authors.initials: JN
authors.lastname: Regan
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Waning
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: tguise@iu.edu.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Guise
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002450:Cell Communication; D006801:Humans; D018908:Muscle Weakness / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta; D002118:Calcium
keywords: Bone; Calcium handling; Skeletal muscle; TGF-β