| First Author | Morozzi G | Year | 2017 |
| Journal | Cell Death Differ | Volume | 24 |
| Issue | 12 | Pages | 2077-2088 |
| PubMed ID | 28885620 | Mgi Jnum | J:268190 |
| Mgi Id | MGI:6269883 | Doi | 10.1038/cdd.2017.132 |
| Citation | Morozzi G, et al. (2017) Oxidative stress-induced S100B accumulation converts myoblasts into brown adipocytes via an NF-kappaB/YY1/miR-133 axis and NF-kappaB/YY1/BMP-7 axis. Cell Death Differ 24(12):2077-2088 |
| abstractText | Muscles of sarcopenic people show hypotrophic myofibers and infiltration with adipose and, at later stages, fibrotic tissue. The origin of infiltrating adipocytes resides in fibro-adipogenic precursors and nonmyogenic mesenchymal progenitor cells, and in satellite cells, the adult stem cells of skeletal muscles. Myoblasts and brown adipocytes share a common Myf5(+) progenitor cell: the cell fate depends on levels of bone morphogenetic protein 7 (BMP-7), a TGF-beta family member. S100B, a Ca(2+)-binding protein of the EF-hand type, is expressed at relatively high levels in myoblasts from sarcopenic humans and exerts anti-myogenic effects via NF-kappaB-dependent inhibition of MyoD, a myogenic transcription factor acting upstream of the essential myogenic factor, myogenin. Adipogenesis requires high levels of ROS, and myoblasts of sarcopenic subjects show elevated ROS levels. Here we show that: (1) ROS overproduction in myoblasts results in upregulation of S100B levels via NF-kappaB activation; and (2) ROS/NF-kappaB-induced accumulation of S100B causes myoblast transition into brown adipocytes. S100B activates an NF-kappaB/Ying Yang 1 axis that negatively regulates the promyogenic and anti-adipogenic miR-133 with resultant accumulation of the brown adipogenic transcription regulator, PRDM-16. S100B also upregulates BMP-7 via NF-kappaB/Ying Yang 1 with resultant BMP-7 autocrine activity. Interestingly, myoblasts from sarcopenic humans show features of brown adipocytes. We also show that S100B levels and NF-kappaB activity are elevated in brown adipocytes obtained by culturing myoblasts in adipocyte differentiation medium and that S100B knockdown or NF-kappaB inhibition in myoblast-derived brown adipocytes reconverts them into fusion-competent myoblasts. At last, interstitial cells and, unexpectedly, a subpopulation of myofibers in muscles of geriatric but not young mice co-express S100B and the brown adipocyte marker, uncoupling protein-1. These results suggest that S100B is an important intracellular molecular signal regulating Myf5(+) progenitor cell differentiation into fusion-competent myoblasts or brown adipocytes depending on its levels. |
