(535e) Regulation of Mesenchymal Stem Cell Myogenic Differentiation by Cell-Cell Adhesion: The Role of Cadherins In Differentiation

Regulation
of mesenchymal stem cell myogenic
differentiation by cell-cell adhesion: the role of cadherins
in differentiation

Stella Alimperti¹ and Stelios Andreadis^1,2

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.