Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells

• Published in: PloS one 2013-02, Vol.8 (2), p.e56641-e56641
• Main Authors: Oishi, Teruyo, Uezumi, Akiyoshi, Kanaji, Arihiko, Yamamoto, Naoki, Yamaguchi, Asami, Yamada, Harumoto, Tsuchida, Kunihiro
• Format: Article
• Language: English
• Subjects: Aberration; Adult; Age; Aged; Aged, 80 and over; Analysis; Animals; Biocompatibility; Biological activity; Biology; Biomedical materials; Bone growth; CD56 antigen; CD56 Antigen - metabolism; Cell Differentiation - genetics; Cells (biology); Differentiation; Humans; Joint surgery; Kinases; Laboratories; Male; Medicine; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Muscle Development - genetics; Muscle, Skeletal - cytology; Muscles; Musculoskeletal system; Nonsteroidal anti-inflammatory drugs; Ossification (ectopic); Osteogenesis; Osteogenesis - genetics; Osteoprogenitor cells; Polymerase chain reaction; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Rodents; Skeletal muscle; Stem cells; Surgery; Transcriptome; Trauma
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056641

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.