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Differentiation. 2018 May - Jun;101:1-7. doi: 10.1016/j.diff.2018.03.001. Epub 2018 Mar 15.

Vitamin C-linker-conjugated tripeptide AHK stimulates BMP-2-induced osteogenic differentiation of mouse myoblast C2C12 cells.

Author information

1
Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea. Electronic address: 96k620@gmail.com.
2
Department of Integrated Material's Development, CHA Meditech Co., Ltd, Daejeon 34025, Republic of Korea. Electronic address: pky@chamc.co.kr.
3
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul 03722, Republic of Korea. Electronic address: olyoula@gmail.com.
4
Department of Preventive Medicine, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea. Electronic address: mira@eulji.ac.kr.
5
Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea. Electronic address: yeon@eulji.ac.kr.

Abstract

Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of Vitamin C-conjugated tripeptides, which were originally developed as a component of a product for collagen synthesis enhancement or human dermal fibroblast growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C-AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline phosphatase, a typical marker of osteoblast differentiation. Vit C-AHK also stimulated the phosphorylation and translocation of Smad1/5/8 to the nucleus and phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and p38. In addition, Vit C-AHK enhanced the BMP-2-induced mRNA expression of osteoblast differentiation-related genes such as ALP, BMP-2, Osteocalcin, and Runx2. Our results suggest that Vit C-AHK exerts an enhancing effect on osteoblast proliferation and differentiation through activation of Smad1/5/8 and MAPK ERK1/2 and p38 signaling and without significant cytotoxicity. These results provide important data for the development of peptide-based bone-regenerative agents and treatment of bone-related disorders.

KEYWORDS:

ALP; BMP-2; MAPK; Osteoblast differentiation; Smad1/5/8; Vit C-AHK

PMID:
29567599
DOI:
10.1016/j.diff.2018.03.001
[Indexed for MEDLINE]

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