Tissue Eng Regen Med.  2016 Feb;13(1):47-56. 10.1007/s13770-016-9102-0.

Effect of Fibroblast Growth Factor-2 and Retinoic Acid on Lineage Commitment of Bone Marrow Mesenchymal Stem Cells

• Lim J
• Park EK

• KMID: 2360866
• DOI: http://doi.org/10.1007/s13770-016-9102-0

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.

Keyword

Human bone marrow mesenchymal stem cells; Lineage commitment; Differentiation; Fibroblast growth factor-2; Retinoic acid

MeSH Terms

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*
Adiponectin
Alkaline Phosphatase
Antigens, Differentiation
Calcium
Fibroblast Growth Factor 2
Osteocalcin
Peroxisome Proliferator-Activated Receptors
Tretinoin