title: Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age.
abstract: Conditional deletion of Mbtps1 (cKO) protease in bone osteocytes leads to an age-related increase in mass (12%) and in contractile force (30%) in adult slow twitch soleus muscles (SOL) with no effect on fast twitch extensor digitorum longus muscles. Surprisingly, bone from 10-12-month-old cKO animals was indistinguishable from controls in size, density, and morphology except for a 25% increase in stiffness. cKO SOL exhibited increased expression of Pax7, Myog, Myod1, Notch, and Myh3 and 6-fold more centralized nuclei, characteristics of postnatal regenerating muscle, but only in type I myosin heavy chain-expressing cells. Increased expression of gene pathways mediating EGF receptor signaling, circadian exercise, striated muscle contraction, and lipid and carbohydrate oxidative metabolism were also observed in cKO SOL. This muscle phenotype was not observed in 3-month-old mice. Although Mbtps1 mRNA and protein expression was reduced in cKO bone osteocytes, no differences in Mbtps1 or cre recombinase expression were observed in cKO SOL, explaining this age-related phenotype. Understanding bone-muscle cross-talk may provide a fresh and novel approach to prevention and treatment of age-related muscle loss.
authors.affiliation: From the Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City Center of Excellence in the Study of Dental and Musculoskeletal Tissues, School of Dentistry, gorskij@umkc.edu.
authors.forename: Jeff P
authors.initials: JP
authors.lastname: Gorski
authors.affiliation: From the Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City Center of Excellence in the Study of Dental and Musculoskeletal Tissues, School of Dentistry.
authors.forename: Nichole T
authors.initials: NT
authors.lastname: Huffman
authors.affiliation: Muscle Biology Research Group, School of Nursing and Health Studies, and.
authors.forename: Julian
authors.initials: J
authors.lastname: Vallejo
authors.affiliation: Muscle Biology Research Group, School of Nursing and Health Studies, and.
authors.forename: Leticia
authors.initials: L
authors.lastname: Brotto
authors.affiliation: Center for Functional Genomics, University at Albany, Rensselaer, New York 12144.
authors.forename: Sridar V
authors.initials: SV
authors.lastname: Chittur
authors.affiliation: Maine Medical Center, Portland, Maine 04102.
authors.forename: Anne
authors.initials: A
authors.lastname: Breggia
authors.affiliation: School of Computing and Engineering, University of Missouri-Kansas City, Kansas City, Missouri 64108, Engineering Systems, Inc., Charlotte, North Carolina 28277, and.
authors.forename: Amber
authors.initials: A
authors.lastname: Stern
authors.affiliation: Muscle Biology Research Group, School of Nursing and Health Studies, and.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Muscle Biology Research Group, School of Nursing and Health Studies, and.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Mo
authors.affiliation: Institut de Recherches Cliniques Montreal, Montreal, Quebec H2W IR7, Canada.
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.affiliation: From the Department of Oral and Craniofacial Sciences, University of Missouri-Kansas City Center of Excellence in the Study of Dental and Musculoskeletal Tissues, School of Dentistry.
authors.forename: Lynda
authors.initials: L
authors.lastname: Bonewald
authors.affiliation: Muscle Biology Research Group, School of Nursing and Health Studies, and.
authors.forename: Marco
authors.initials: M
authors.lastname: Brotto
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D018345:Mice, Knockout; D009119:Muscle Contraction; D024510:Muscle Development; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D041641:Musculoskeletal Development; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D010011:Osteocytes / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D055948:Sarcopenia / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1
keywords: DMP1; MBTPS1; bone; cell signaling; centralized nuclei; cross-talk; gene knock-out; osteocyte; regeneration; skeletal muscle