Role of LATS kinase on the mesenchymal stem cells differentiation to chondrocytes

Abstract

The Hippo signalling pathway is important for controlling the organ size and tissue homeostasis. The non-canonical Hippo pathway was shown to control the osteogenesis and adipogenesis of Mesenchymal stem cells (MSCs). However, their role in chondrogenesis is poorly disclosed. Therefore, this present study aims to investigate the role of LATS kinase, one of the Hippo pathway core-kinases, on MSC differentiation to chondrocytes. Lysophosphatidic acid (LPA) was used to modulate the expression of LATS in placenta and chorion-derived MSCs at different time points during chondrogenic induction. The differentiation result was assessed by the expression of chondrogenic specific genes and proteins. The treatment of MSCs with LPA result in the reduced LATS1 and LATS2 protein expressions in the dose-dependent manners. The cell from all treatments can be differentiated to chondrocytes. However, the significant down-regulation of MSCs specific marker and the up-regulation of chondrocyte-related gene were found in the LPA treated cells when compared to the non-treated control. Interestingly, chondrocyte specific collagen Type II (COL2A1) was significantly increased in the LPA-treated cells. This result suggests that the inhibition of LATS kinase enhances chondrogenic differentiation of MSCs. The result of this finding could be beneficial to the patients with cartilage degeneration.