CMTM8 is a suppressor of human mesenchymal stem cell osteogenic differentiation and promoter of proliferation via EGFR signalling

Abstract

Multipotent bone marrow-derived mesenchymal stem/ stromal cells (BMSC) exhibit a finite lifespan following ex vivo expansion leading to cellular senescence. Many factors can contribute to this. Recently, our group has identified for the first time expression of the chemokine-like factor superfamily 8 (CMTM8) gene in cultured human BMSC. In the present study, we examine the role of CMTM8 in BMSC proliferation, migration and differentiation. Functional studies using siRNA mediated knockdown of CMTM8 in human BMSC resulted in decreased capacity to undergo proliferation and migration and an increased capacity for osteogenic differentiation in vitro. Furthermore, reduced CMTM8 levels led to a decrease in the EGFR signalling pathway during BMSC proliferation and migration respectively. Supportive studies using retroviral mediated enforced expression of CMTM8 in BMSC resulted in an increased capacity for proliferation and migration but a decreased osteogenic differentiation potential. Collectively, these data suggest that CMTM8 promotes BMSC proliferation and BMSC migration via the EGFR/ ERK1/2 pathway. This study provides insight into novel regulatory mechanisms of human BMSC growth and cell fate determination.