Effect of Fibroblast Growth Factor-2 and Retinoic Acid on Lineage Commitment of Bone Marrow Mesenchymal Stem Cells.
10.1007/s13770-016-9102-0
- Author:
Jiwon LIM
1
;
Eui Kyun PARK
Author Information
1. Department of Oral Pathology, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea. epark@knu.ac.kr
- Publication Type:Original Article
- Keywords:
Human bone marrow mesenchymal stem cells;
Lineage commitment;
Differentiation;
Fibroblast growth factor-2;
Retinoic acid
- MeSH:
Adipocytes;
Adiponectin;
Alkaline Phosphatase;
Antigens, Differentiation;
Bone Marrow*;
Calcium;
Fibroblast Growth Factor 2*;
Fibroblasts*;
Hand;
Humans;
Lipid Droplets;
Mesenchymal Stromal Cells*;
Miners;
Osteoblasts;
Osteocalcin;
Peroxisome Proliferator-Activated Receptors;
Peroxisomes;
Stem Cells;
Tretinoin*
- From:
Tissue Engineering and Regenerative Medicine
2016;13(1):47-56
- CountryRepublic of Korea
- Language:English
-
Abstract:
In this study, we examined the effect of a combination of fibroblast growth factor-2 (FGF-2) and retinoic acid (RA) on osteoblast and adipocyte lineage commitment and differentiation of human bone marrow mesenchymal stem cells (BMSCs). Pretreatment of human BMSCs with FGF-2 or RA for 5 days followed by osteoblast differentiation induction showed high calcium deposition compared to control. A combination of FGF-2 and RA further induced calcium deposition compared to FGF-2 or RA alone. The enhanced mineral deposition was accompanied with the increased expression of osteoblast differentiation markers, alkaline phosphatase and osteocalcin. On the other hand, FGF-2 pretreatment followed by adipocyte differentiation induction also showed increased formation of lipid droplets in human BMSCs, whereas RA pretreatment suppressed formation of lipid droplets. However, a combination of FGF-2 and RA increased formation of lipid droplets and expression of adipocyte marker genes, including adiponectin, ADIPOQ, FABP4, peroxisome proliferator-activated receptor γ (PPARγ), and C/EBPα. During pretreatment of BMSCs with FGF-2, RA or in combination, the cells expressed similar levels of MSC surface markers such as CD29, CD44, CD90, and CD105, indicating that they maintain stem cell potential. To determine how RA cooperates with FGF-2 in osteoblast and adipocyte lineage commitment, the expression of RA receptors and intracellular lipid-binding proteins was examined. A combination of FGF-2 and RA strongly induced the expression of RA receptor α, β, γ, PPAR β/δ, CRABP-II, and FABP5. Collectively, these results demonstrate that combined pretreatment of human BMSCs with FGF-2 and RA enhances the commitment into osteoblast and adipocyte lineages through modulation of the expression of RA-related genes.
