Role of Yes-associated protein (YAP) in regulation of mesenchymal stem cell tenogenic differentiation.

The Yes-associated protein (YAP) transcription co-activator is recognized as a key mediator and has been implicated in the regulation of stem cell fate; however, the role of YAP in the tenogenic differentiation of mesenchymal stem cells (MSCs) is not well understood. In the present study, we characterized tenogenic differentiation of C3H10T1/2 cells induced by BMP-12 and evaluated the function of YAP in the regulation of the BMP-12-induced tenogenesis. We found that the tendon-related proteins Scleraxis, Tenascin C, and Tenomodulin were significantly increased after induction by 10 ng/ml BMP-12 for 48 h in C3H10T1/2 cells. In addition, the expression of YAP was significantly enhanced and transferred from the cytoplasm to the nucleus during tenogenic differentiation. In contrast, downregulation of YAP suppressed the cells' tenogenic differentiation, and the expression of YAP transferred from the nucleus to the cytoplasm. These results indicate that YAP is required for the expression of tenogenic markers in the tenocytic differentiation process of C3H10T1/2 cells. Collectively, we demonstrate that YAP transcription co-activator is a novel regulator in the process of BMP-12-induced MSCs tenogenesis and has a correlation with the other tenogenic regulators and markers. These results shed new light on the function of YAP in tendon healing and regeneration.