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Polypeptides IGF-1C and P24 synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells in vitro through the p38 and JNK signaling pathways.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2021 Dec; Vol. 141, pp. 106091. Date of Electronic Publication: 2021 Oct 06. - Publication Year :
- 2021
-
Abstract
- Objectives: Insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein 2 (BMP-2) both promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs). IGF-1C, the C domain peptide of IGF-1, and P24, a BMP-2-derived peptide, both have similar biological activities as their parent growth factors. This study aimed to investigate the effects and mechanisms of polypeptides IGF-1C and P24 on the osteogenic differentiation of BMSCs.<br />Methods: The optimum concentrations of IGF-IC and P24 were explored. The effects of the two polypeptides on BMSC proliferation and osteogenic differentiation were examined using a CCK-8 assay, flow cytometry, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qPCR, and Western blotting. In addition, specific pathway inhibitors were utilized to explore whether the p38 and JNK pathways were involved in this process.<br />Results: The optimal concentration of both polypeptides was 50 μg/ml. IGF-1C and P24 synergistically promoted BMSC proliferation, increased ALP activity and calcified nodule formation, upregulated the mRNA and protein levels of Osx, Runx2, Ocn, Opn, and Col1a1, and improved the phosphorylation levels of p38 and JNK proteins. Inhibition of the pathways significantly reduced p38 and JNK activation and blocked Runx2 expression while inhibiting ALP activity and calcified nodule formation.<br />Conclusions: These findings suggest that IGF-1C and P24 synergistically promote the osteogenesis of BMSCs through activation of the p38 and JNK signaling pathways.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Peptides pharmacology
Peptides metabolism
Bone Morphogenetic Protein 2 metabolism
Bone Morphogenetic Protein 2 genetics
Bone Marrow Cells metabolism
Bone Marrow Cells cytology
Bone Marrow Cells drug effects
Cells, Cultured
Rats, Sprague-Dawley
Rats
Peptide Fragments pharmacology
Peptide Fragments metabolism
Humans
Mesenchymal Stem Cells metabolism
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells drug effects
Osteogenesis drug effects
Insulin-Like Growth Factor I metabolism
Insulin-Like Growth Factor I pharmacology
Cell Differentiation drug effects
MAP Kinase Signaling System drug effects
Cell Proliferation drug effects
p38 Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 141
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 34624508
- Full Text :
- https://doi.org/10.1016/j.biocel.2021.106091