BioProject

In this study, we found that Fgf9 regulates the bone-fat balance by modulating the cell fate determination of BMSCs. More...

In this study, we found that Fgf9 regulates the bone-fat balance by modulating the cell fate determination of BMSCs. Histology and micro-CT analysis demonstrate that Fgf9 S99N mutation (loss-of-function) significantly inhibited the formation of bone marrow adipose tissue (BMAT) in adult mice and alleviated the ovariectomized (OVX) induced bone loss and BMAT accumulation. In vitro cytodifferentiation assays unveiled that the Fgf9 S99N mutation hindered adipogenesis while promoting osteogenesis in BMSCs. Furthermore, recombinant FGF9 stimulation and Fgf9 overexpression in BMSCs demonstrated that Fgf9 significantly promoted adipocyte formation and inhibited osteogenesis in vitro and in vivo. Cytodifferentiation assays at various stages of BMSC differentiation indicated that FGF9 altered the osteogenic and adipogenic potential of BMSCs, particularly during the early stages of differentiation. Transcriptomic and gene expression analyses demonstrated that FGF9 significantly upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. KEEG analysis revealed and in vitro differentiation assays with specific inhibitors confirmed that FGF9 modulated bone-fat balance by inhibiting osteogenesis via the MAPK/ERK pathway and promoting adipogenesis by activating the PI3K/AKT and Hippo pathways. Overall design: To investigate the pivotal mechanism, we performed RNA-seq on 6 groups of BMSCs, which were cultured separately with or without 20 ng/mL FGF9 in culture medium (CM, CM_F9), osteogenic induction medium (OI, OI_F9), and adipogenic induction medium (AI, AI_F9). There are the triplicate samples within every group. Less...