Regulation of mesenchymal stem cell myogenic differentiation by cell-cell adhesion: the role of cadherins in differentiation
Stella Alimperti1 and Stelios Andreadis1,2
1 Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, 14260; 2Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY 14203
During mesenchymal stem cell (MSC) differentiation toward myogenic lineage, early (aSMA), intermediate (calponin) and late (myosin heavy chain, MHC) markers are expressed. It is well known that MSC can be coaxed to the myogenic lineage using soluble factors such as TGF-β1 but cell-cell communication has not been examined in the context of stem cell differentiation. We report that confluency promoted myogenic differentiation of MSC even under conditions that suppressed differentiation e.g. in the presence of bFGF. Specifically, cell-cell contact increased expression of myogenic markers such as αSMA, calponin and smoothelin. Since cell-cell adhesion is mediated by cadherins, we examined how two cadherins namely, N-cadherin or OB-cadherin may affect cell-cell contact mediated MSC differentiation. Here we report that OB-cadherin plays an important role in myogenic differentiation. Gene knockdown studies revealed that OB-cadherin mediated cell proliferation, aSMA expression and smooth muscle cell contraction. The relationship between OB-cadherin and N-cadherin was also examined as well as intracellular signaling pathways and transcription factors such as myocardin and MRTF that may be mediating the signals of cadherin engagement. These results are novel as they identify cell-cell contact as a potent inducer of myogenic differentiation through cadherins and their intracellular mediators.