Abstract

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.

Highlights

  • Collagen peptides (CPs) are formed through the hydrolysis of collagen and are widely used as a functional food [1, 2]

  • Effects of Prolyl-hydroxyprolineFoxo1Forkhead box O1 (Pro-Hyp) on ALP activity in Forkhead box O1 (Foxo1)-knockdown cells we examined the effect of Pro-Hyp on alkaline phosphatase (ALP) activity to investigate Pro-Hyp influence on osteoblast differentiation in Foxo1-knockdown cells

  • In this study, we focused on Foxo1 and Forkhead box G1 (Foxg1) proteins and aimed to reveal the osteoblast differentiation control mechanisms of Pro-Hyp

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Summary

Introduction

Collagen peptides (CPs) are formed through the hydrolysis of collagen and are widely used as a functional food [1, 2]. The effects of CPs on bone metabolism were reported [5,6,7]. Wu et al reported that CPs improve bone mineral density in rats fed a calcium-deficient diet [8]. Oral administration of CPs to ovariectomized rats or mice was shown to increase bone strength and bone mass [9,10,11]. These reports show that CP plays an important role in bone metabolism

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