title: Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
abstract: Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+) and PDGFRα(+) cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+) cells and PDGFRα(+) cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+) cells formed bone-like tissue and showed successful engraftment, while CD56(+) cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+) cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs) are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+) cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+) cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+) cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+) cells. Our results suggest that PDGFRα(+) cells may be the major source of HO and that the newly identified miRNAs may regulate osteogenic differentiation process of PDGFRα(+) cells.
authors: Department of Orthopaedic Surgery, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
authors: Teruyo
authors: T
authors: Oishi
authors: Akiyoshi
authors: A
authors: Uezumi
authors: Arihiko
authors: A
authors: Kanaji
authors: Naoki
authors: N
authors: Yamamoto
authors: Asami
authors: A
authors: Yamaguchi
authors: Harumoto
authors: H
authors: Yamada
authors: Kunihiro
authors: K
authors: Tsuchida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D059467:Transcriptome
chemical_list: D019002:CD56 Antigen; D035683:MicroRNAs; D020796:Receptor, Platelet-Derived Growth Factor alpha