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Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):371-7. doi: 10.1016/j.bbrc.2014.11.025. Epub 2014 Nov 15.

COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways.

Author information

1
Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, South Korea.
2
School of Dentistry and Dental Research Institute, Seoul National University, Seoul, South Korea.
3
College of Veterinary Medicine, Chonbuk National University, Jeonju, South Korea.
4
Research Institute of Biotechnology, Dongguk University, Seoul, South Korea.
5
Cluster for Craniofacial Development & Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, South Korea. Electronic address: leejc88@jbnu.ac.kr.

Abstract

Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentials of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways.

KEYWORDS:

COMP-Ang1; Mesenchymal stem cells; Migration; PI3K/Akt; Tie-2

PMID:
25446117
DOI:
10.1016/j.bbrc.2014.11.025
[Indexed for MEDLINE]

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