engleski

Characterization of aSMA Expressing Cells That Contribute To Muscle Heterotopic Ossification

Heterotopic ossification (HO) is a pathological process in which bone tissue forms in soft connective tissues such as muscle. There are no proven pharmacological treatments available for the prevention of HO. Previous studies have suggested that muscle-resident non-myogenic mesenchymal progenitors are likely to be the source of osteoblasts and chondrocytes in the lesions. However, the previously used markers label only up to half of the cells within the lesions, suggesting that other cell populations that contribute to HO are yet to be identified. We have previously identified alpha smooth muscle actin (αSMA) as a marker of osteogenic progenitor cells in bone and periodontium, and osteo-chondro progenitors in the periosteum during fracture healing. We therefore evaluated whether αSMACreERT2 identified osteoprogenitors in the muscle. We show that in the muscle, αSMACreERT2 labels both perivascular cells, and SM/C2.6+ satellite cells that contribute to muscle fiber growth. αSMACre-labeled cells are capable of osteogenic differentiation in vitro and make a significant contribution to osteoblasts and chondrocytes in BMP2-induced lesions in vivo. The differentiation of Pax7CreERT2-labeled muscle satellite cells was evaluated in parallel, indicating that they are restricted to myogenic differentiation in vitro, and only rarely contribute to heterotopic lesions in vivo. However, after release from their niche, and transplantation with BMP2, satellite cells labeled by both αSMA and Pax7 could differentiate into osteoblasts. Our data indicate that αSMACreERT2 labels a large proportion of osteoprogenitors in muscle, and that muscle satellite cells can contribute to bone formation in vivo with sufficient stimulation.

heterotopic ossification; muscle progenitor cells; mesenchymal progenitor cells

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