Role of fibroblast growth factor receptors (FGFR) and FGFR like-1 (FGFRL1) in mesenchymal stromal cell differentiation to osteoblasts and adipocytes

Abstract

<div><p><a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fibroblast-growth-factor" title="Learn more about Fibroblast growth factor">Fibroblast growth factors</a> (FGF) and their receptors (FGFRs) regulate many developmental processes including differentiation of <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mesenchyme" title="Learn more about Mesenchyme">mesenchymal</a> <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/stromal-cell" title="Learn more about Stromal cell">stromal cells</a> (MSC). We developed two <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/msc-gene" title="Learn more about MSC (gene)">MSC</a> lines capable of differentiating to <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/osteoblast" title="Learn more about Osteoblast">osteoblasts</a> and <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/adipocyte" title="Learn more about Adipocyte">adipocytes</a> and studied the role of <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fibroblast-growth-factor-receptor" title="Learn more about Fibroblast growth factor receptor">FGFRs</a> in this process. We identified <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fibroblast-growth-factor-receptor-2" title="Learn more about Fibroblast growth factor receptor 2">FGFR2</a> and <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fibroblast-growth-factor-receptor-like-1" title="Learn more about Fibroblast growth factor receptor-like 1">fibroblast growth factor receptor like-1</a> (FGFRL1) as possible actors in MSC differentiation with <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/dna-microarray" title="Learn more about DNA microarray">gene microarray</a> and qRT-PCR. FGFR2 and <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fibroblast-growth-factor-receptor-like-1" title="Learn more about Fibroblast growth factor receptor-like 1">FGFRL1</a> <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/messenger-rna" title="Learn more about Messenger RNA">mRNA</a> expression strongly increased during MSC differentiation to osteoblasts. <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/basic-fibroblast-growth-factor" title="Learn more about Basic fibroblast growth factor">FGF2</a> treatment, resulting in <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/downregulation-and-upregulation" title="Learn more about Downregulation and upregulation">downregulation</a> of FGFR2, or silencing FGFR2 expression with siRNAs inhibited osteoblast differentiation. During adipocyte differentiation expression of <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fibroblast-growth-factor-receptor-1" title="Learn more about Fibroblast growth factor receptor 1">FGFR1</a> and FGFRL1 increased and was down-regulated by FGF2. FGFR1 knockdown inhibited adipocyte differentiation. Silencing FGFR2 and FGFR1 in MSCs was associated with decreased FGFRL1 expression in osteoblasts and adipocytes, respectively. Our results suggest that FGFR1 and FGFR2 regulate FGFRL1 expression. FGFRL1 may mediate or modulate FGFR regulation of MSC differentiation together with FGFR2 in osteoblastic and FGFR1 in adipocytic <a href="http://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lineage-genetic" title="Learn more about Lineage (genetic)">lineage</a>.</p></div>