title: Age-related resistance of skeletal muscle-derived progenitor cells to SPARC may explain a shift from myogenesis to adipogenesis.
abstract: Aging causes phenotypic changes in skeletal muscle progenitor cells (SMPCs) that lead to the loss of myogenicity and adipogenesis. Secreted protein acidic and rich in cysteine (SPARC), which is secreted from SMPCs, stimulates myogenesis and inhibits adipogenesis. The present study aimed to examine whether changes in SPARC expression, its signaling pathway, or both are involved in age-related phenotypic changes in SMPCs. SPARC expression levels were comparable in SMPCs derived from young and old rats. However, when SPARC expression was reduced by a SPARC-specific siRNA, SMPCs from young rats showed reduced myogenesis and increased adipogenesis. In striking contrast, old rats showed little changes in these functions. Recombinant SPARC was effective in inhibiting adipogenesis and promoting myogenesis of SMPCs from young rats but had no effect on SMPCs from old rats when endogenous SPARC levels were reduced by the SPARC-siRNA. Further, the level of integrin α5, a subunit of the putative SPARC receptor, was decreased in SMPCs from old rats, and its inhibition in SMPCs from young rats by siRNA reduced adipogenesis in response to SPARC. These results suggest that, although SPARC plays a role in regulating SMPC function, SMPCs become refractory to the action of SPARC with age. Our data may explain an age-related shift from myogenesis to adipogenesis, associated with sarcopenia.
authors.affiliation: Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nakano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamanouchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuwaki
authors.forename: Masugi
authors.initials: M
authors.lastname: Nishihara
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D015398:Signal Transduction
chemical_list: D016023:Integrins; D015676:Osteonectin; D034741:RNA, Small Interfering