Mechanobiology June 26th - June 2nd 2016

Mechanobiology: June 26th  - June 2nd 2016

Cadherin-11 regulates mesenchymal stem cell differentiation into smooth muscle cells and development of contractile function in vivo
Stella Alimperti, Hui You, Teresa George, Sandeep K. Agarwal, Stelios T. Andreadis


Although soluble factors (e.g. Transform Growth Factor beta 1 (TGF-β1)) induced mesenchymal stem cell (MSC) differentiation toward smooth muscle (SMC) lineage, the role of adherent junctions in this process is not well understood. We found that Cadherin-11 but not Cadherin-2 was necessary for MSC differentiation into SMC. Cadherin-11 regulated expression of TGF-β1 and affected SMC differentiation through a TGF-β receptor II (TGFβRII) dependent but Smad2/3 independent pathway. In addition, Cadherin-11 activated the serum response factor (SRF) and SMC proteins via the Rho-associated protein kinase (ROCK) pathway. Engagement of Cadherin-11 increased its own expression through SRF, suggesting the presence of an auto regulatory feedback loop that committed MSC to SMC fate. Notably, SMC-containing tissues such as aorta and bladder from Cadherin-11 null mice (Cdh11−/−) mice showed significantly reduced levels of SMC proteins and exhibited diminished contractility. This is the first report implicating Cadherin-11 in SMC differentiation and contractile function in vitro as well as in vivo.