关键词: DMP1 MBTPS1 bone cell signaling centralized nuclei cross-talk gene knock-out osteocyte regeneration skeletal muscle

Mesh : Animals Crosses, Genetic Energy Metabolism Gene Expression Profiling Gene Expression Regulation, Developmental Male Mice, Knockout Muscle Contraction Muscle Development Muscle Fibers, Slow-Twitch / metabolism pathology Muscle Strength Muscle, Skeletal / metabolism pathology Musculoskeletal Development Myogenic Regulatory Factors / genetics metabolism Osteocytes / enzymology metabolism pathology Proprotein Convertases / genetics metabolism RNA, Messenger / metabolism Sarcopenia / metabolism pathology Serine Endopeptidases / genetics metabolism Transcription Factors / genetics metabolism

来  源:   DOI:10.1074/jbc.M115.686626

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.
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