Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado-shi, Saitama, 350-0295 Japan.
Nitta Gelatin Inc., Peptide Division, 2-22 Futamata, Yao, Osaka, 581-0024 Japan.
Cell Mol Biol Lett. 2017 Dec 1;22:27. doi: 10.1186/s11658-017-0060-2. eCollection 2017.
Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. We previously reported that Pro-Hyp promotes the differentiation of osteoblasts by increasing Runx2, osterix and Col1α1 mRNA expression levels. Here, to elucidate the mechanism of Pro-Hyp promotion of osteoblast differentiation, we focus on the involvement of Foxo1 in osteoblast differentiation via Runx2 regulation and the role of Foxg1 in Foxo1 regulation. The addition of Pro-Hyp had no effect on MC3T3-E1 cell proliferation in Foxo1- or Foxg1-knockdown cells. In Foxo1-knockdown cells, the addition of Pro-Hyp increased ALP activity, but in Foxg1-knockdown cells, it had no effect on ALP activity. An enhancing effect of Pro-Hyp on the Runx2 and osterix expression levels was observed in Foxo1-knockdown cells. However, no enhancing effect of Pro-Hyp on osteoblastic gene expression was observed when Foxg1 was knocked down. These results demonstrate that Pro-Hyp promotes osteoblastic MC3T3-E1 cell differentiation and upregulation of osteogenic genes via Foxg1 expression.
脯氨酰-羟脯氨酸（Pro-Hyp）是胶原蛋白衍生二肽的主要成分之一。我们之前报道过 Pro-Hyp 通过增加 Runx2、osterix 和 Col1α1 mRNA 表达水平促进成骨细胞分化。在这里，为了阐明 Pro-Hyp 促进成骨细胞分化的机制，我们重点研究了 Foxo1 通过 Runx2 调节在成骨细胞分化中的作用，以及 Foxg1 在 Foxo1 调节中的作用。Pro-Hyp 的添加对 Foxo1 或 Foxg1 敲低细胞中的 MC3T3-E1 细胞增殖没有影响。在 Foxo1 敲低细胞中，添加 Pro-Hyp 增加了 ALP 活性，但在 Foxg1 敲低细胞中，它对 ALP 活性没有影响。在 Foxo1 敲低细胞中观察到 Pro-Hyp 对 Runx2 和 osterix 表达水平的增强作用。然而，当敲低 Foxg1 时，Pro-Hyp 对成骨基因表达没有增强作用。这些结果表明 Pro-Hyp 通过 Foxg1 表达促进成骨 MC3T3-E1 细胞分化和上调成骨基因。
