Session: SUN 649-677-Adipocyte Biology
Poster Board SUN-655
While changes in cell morphology and cytoskeletal integrity can alter pre-committed mesenchymal stem cell differentiation of certain lineages, previous studies have shown that the morphological changes can also affect the early commitment of pluripotent mesenchymal stem cells via modulation of RhoA activity. The RhoA pathway regulates actin polymerization dynamics through various effectors including Rho-associated kinases (ROCKs) and Actin Binding Proteins (ABPs) to promote the incorporation of Globular-actin (G-actin) into Filament-actin (F-actin). In doing so, Myocardin-related transcription factors (MRTFs) bound with G-actin are released for nuclear import to co-activate Serum Response Factor (SRF) cytoskeletal target genes. Exactly how the RhoA-actin-MRTF-SRF circuit is involved in the regulation of early commitment of mesenchymal stem cells is still poorly understood.
In this study, the role of the MRTFA/SRF-actin circuit in the commitment of mesenchymal stem cells into adipogenic versus osteogenic lineages has been investigated. Preliminary results showed that MRTFA and SRF inhibits adipogenesis and enhances osteogenesis in murine pluripotent MSCs, whereas dominant-negative MRTFA and SRF had the opposite effects. Bone marrow stem cells isolated from global MRTFA knockout mice showed increased adipogenesis and compromised osteogenesis when compared to WT littermates. The SRF inhibitor, CCG1423, mimicked the effects of knocking out MRTFA in WT mouse bone marrow stem cells by inhibiting osteogenesis and promoting adipogenesis. MRTFA and SRF appear to be crucial regulators of the balance between adipogenic and osteogenic differentiation of the mesenchymal stem cells.
Nothing to Disclose: HB, SRF
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