GH prevents adipogenic differentiation of mesenchymal stromal stem cells derived from human trabecular bone via canonical Wnt signaling

摘要

The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBP alpha) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA). In parallel, GH induced an increase in the gene expression and protein levels of osterix (OSX) and osteoprotegerin (OPG). These effects were ascribed to enhanced Wnt signaling as GH significantly reduced Wnt inhibitors, Dickkopf 1 (DKK1) and the secreted frizzled protein 2 (SFRP2), and increased the expression of an activator of Wnt, Wnt3. Accordingly, the expression of beta-catenin and its nuclear levels were raised. Wnt involvement in GH anti-adipogenic effect was further confirmed by the silencing of beta-catenin. In silenced hMSC, both the inhibitory effect of GH on the expression of the adipogenic genes, ADN and C/EBP alpha and the lipogenesis enzymes LPL and ACACA, were prevented together with the stimulatory effect of GH on the osteogenic genes OSX and OPG.