Multipotent bone marrow-derived mesenchymal stem/stromal cells (BMSCs) exhibit a finite life span after 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 BMSCs. In this study, we examine the role of CMTM8 in BMSC proliferation, migration, and differentiation. Functional studies using siRNA-mediated knockdown of CMTM8 in human BMSCs 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 epidermal growth factor receptor (EGFR) signaling 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 through the EGFR/ERK1/2 pathway. This study provides insight into novel regulatory mechanisms of human BMSC growth and cell fate determination.

中文翻译：

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CMTM8是人类间充质干细胞成骨细胞分化和通过EGFR信号传导促进增殖的抑制剂。

多能骨髓来源的间充质干/基质细胞（BMSC）在离体扩增导致细胞衰老后显示有限的寿命。许多因素可以导致此。最近，我们小组首次在培养的人骨髓间充质干细胞中鉴定了趋化因子样因子超家族8（CMTM8）基因的表达。在这项研究中，我们检查了CMTM8在BMSC增殖，迁移和分化中的作用。在人BMSC中使用siRNA介导的CMTM8敲低的功能研究导致体外增殖和迁移的能力降低，成骨分化的能力增强。此外，减少了CMTM8分别导致BMSC增殖和迁移过程中表皮生长因子受体（EGFR）信号传导途径的减少。在BMSC中使用逆转录病毒介导的CMTM8强制表达的支持性研究导致增殖和迁移能力增强，但成骨分化潜能降低。总的来说，这些数据表明CMTM8通过EGFR / ERK1 / 2途径促进BMSC增殖和BMSC迁移。这项研究提供了人类BMSC生长和细胞命运确定的新​​型调控机制的见解。