miR106b inhibition improves myogenic regenerative capacity of murine and human muscle stem cells and attenuates muscular dystrophy phenotype

Satellite cells (SCs), the skeletal muscle stem cells, display functional heterogeneity linked to their regenerative potential. Dramatic changes in their behaviour are also associated to muscle wasting diseases. Therefore, understanding the mechanisms controlling satellite cell heterogeneous behaviour during muscle regeneration and diseases has become increasingly important for regenerative medicine. Here, we show that miR-106bis expressed in Myf5- quiescent SCs and downregulated during SC activation and muscle regeneration. In vitro and in vivo studies to show that miR106b inhibition enhances the regenerative capability of murine and human SCs by increasing myogenic precursors. miR106b is increased in dystrophic mice and intramuscular injection of antimiR enhances muscle regeneration accompanied by significant functional recovery. miR-106b is also elevated in human dystrophic SCs and its inhibition improves intrinsic proliferative defects, increasing their myogenic differentiation potential. Therefore, this study identifies miR-106b as compelling candidate to consider for potential clinical studies. Overall design: In order to analyze expression profile changes as a result of miR106b inhibition during muscle regeneration in DMD mice model, cardiotoxin along either with anti-miR106b or with anti-miR-Scrambled control were injected in tibialis anterior muscles. Samples were collected 3 or 5 days after injection. Each experimental point is represented by an animal tripilcate. AD3 represents 3 days post-injection of anti-miR106b treatment experimetal points (n=3), CD3 represents 3 days post-injection of anti-Scrambled control experimetal points (n=3), AD7 represents 7 days post-injection of anti-miR106b treatment experimetal points (n=3), CD7 represents 7 days post-injection of anti-Scrambled control experimetal points (n=3). Therefore, the number of samples(experimental points) is 12.