Objectives: Growth differentiation factor 11 (GDF11), an emerging secreted member of the TGF-beta superfamily, plays essential roles in development, physiology and multiple diseases; however, its role during adipogenic differentiation and the underlying mechanisms remains poorly understood.
Materials and methods: Bone marrow-derived human mesenchymal stem cells (hMSCs) and 3T3-L1 pre-adipocytes were induced with adipogenic culture medium supplementing with different concentrations of recombinant GDF11 (rGDF11 0, 10, 50, 100 ng mL-1 ). Oil Red O staining, qRT-PCR analysis, Western blot analysis and immunofluorescence staining were performed to assay adipogenesis.
Results: For both hMSCs and 3T3-L1 pre-adipocytes, the presence of rGDF11 leads to a dose-dependent reduction of intracellular lipid droplet accumulation and suppressed adipogenic-related gene expression. Mechanically, GDF11 inhibits adipogenesis by activating Smad2/3-dependent TGF-beta signalling pathway, and these inhibitory effects could be restored by SB-431542, a pharmacological TGF-beta type I receptor inhibitor.
Conclusions: Taken together, our data indicates that GDF11 inhibits adipogenic differentiation in both hMSCs and 3T3-L1 pre-adipocytes by activating Smad2/3-dependent TGF-beta signalling pathway.
Keywords: 3T3-L1 pre-adipocytes; TGF-beta; adipogenesis; growth differentiation factor 11; mesenchymal stem cells.
© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.