Elucidation of mechanisms underlying regulation of proliferation and differentiation of mesenchymal stem cells derived from periodontal ligament

为探讨牙周膜间充质干细胞（mesenchymal stem cells，MSCs）增殖和分化的分子调控机制，我们建立了两种大鼠牙周膜细胞的单细胞来源培养物（single cell-derived cultures，SCDC），其中一种称为SCDC 2，具有自我更新和多能性，另一种称为SCDC 1，不具有自我更新和多能性。然后，我们综合比较了SCDC 1和SCDC 2的基因表达状态和细胞内分子的磷酸化状态。我们发现，在54，000个靶基因中，约600个基因被鉴定为两种细胞之间的差异表达基因。特别是，我们发现，一些转录因子，这是以前报道的几种干细胞的增殖和分化调节因子，在SCDC 2细胞中的高表达。此外，我们还发现FGF和TGF-β诱导的细胞内信号在MSCs增殖和分化的调控中起重要作用。因此，我们成功地阐明了调控PDL来源的MSC增殖和分化的分子机制。

To elucidate molecular mechanisms underlying the regulation of proliferation and differentiation of mesenchymal stem cells (MSCs) derived from periodontal ligament (PDL), we established two types of single cell-derived cultures (SCDCs) of rat ligament cells, one of which named as SCDC2 retained the ability of self-renewal and multipotency and another of which named as SCDC1 did not. Then, we comprehensively compared the genes expression status and phosphorylation status of intracellular molecules between SCDC1 and SCDC2. We found that among 54,000 target genes, around 600 genes were identified as differentially expressed genes between the two types of cells. In particular, we found that some transcription factors, which were previously reported as proliferation and differentiation regulators of several kinds of stem cells, were highly expressed in the SCDC2 cells. Moreover, we found that the FGF-induced- and TGF--induced-intracellular signaling played important roles on the regulation of proliferation and differentiation of the MSCs. Thus, we successfully elucidated the molecular mechanisms underlying the regulation of proliferation and differentiation of MSCs derived from PDL.