The effects of TGFBR3 on adipogenesis of FAPs

Platelet-rich plasma (PRP) is used to treat musculoskeletal diseases, such as rotator cuff tears, and has been proven to attenuate fatty infiltration in muscle injury; however, the effective components are still unclear. Furthermore, PRP is currently strictly used by donors in themselves, and it is unknown whether and how the heterogeneity of donors, especially aging, would change the composition of PRP and impact the therapeutic effects. In this study, we found that young donor-derived exosomes, but not those from old people, were critical components in PRP that regulate fatty infiltration in muscle injury by directly inhibiting adipogenesis of muscle-resident FAPs. The characteristics of young donor-derived PRP exosomes were quite different from those of old donor-derived PRP exosomes. Mechanistically, we demonstrated that two components of miRNA cargo, hsa-let-7f-5p and hsa-miR-16-5p, played an essential role in regulating adipogenesis of FAPs and fatty infiltration by targeting TGFBR3. Overall design: RNA-seq profiling of FAPs were transfected with TGFBR3 overexpressing plasmids or vectors and then were cultured in adipogenic induction medium.