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

• Published in: Molecular and cellular endocrinology Vol. 461; pp. 194 - 204
• Main Authors: Kähkönen, T.E., Ivaska, K.K., Jiang, M., Büki, K.G., Väänänen, H.K., Härkönen, P.L.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 05-02-2018
• Subjects: Adipocyte; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Animals; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Line; Down-Regulation - drug effects; Fibroblast growth factor; Fibroblast Growth Factor 2 - pharmacology; Fibroblast growth factor receptor; Fibroblast growth factor receptor like-1; Gene Expression Profiling; Gene Silencing; Male; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mesenchymal stromal cell; Mice, Inbred C57BL; Osteoblast; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Receptor, Fibroblast Growth Factor, Type 5 - genetics; Receptor, Fibroblast Growth Factor, Type 5 - metabolism; Receptors, Fibroblast Growth Factor - genetics; Receptors, Fibroblast Growth Factor - metabolism; Osteoblast; Adipocyte; Fibroblast growth factor; Mesenchymal stromal cell; Fibroblast growth factor receptor like-1; Fibroblast growth factor receptor
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2017.09.015

Fibroblast growth factors (FGF) and their receptors (FGFRs) regulate many developmental processes including differentiation of mesenchymal stromal cells (MSC). We developed two MSC lines capable of differentiating to osteoblasts and adipocytes and studied the role of FGFRs in this process. We identified FGFR2 and fibroblast growth factor receptor like-1 (FGFRL1) as possible actors in MSC differentiation with gene microarray and qRT-PCR. FGFR2 and FGFRL1 mRNA expression strongly increased during MSC differentiation to osteoblasts. FGF2 treatment, resulting in downregulation of FGFR2, or silencing FGFR2 expression with siRNAs inhibited osteoblast differentiation. During adipocyte differentiation expression of FGFR1 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 lineage.
•Immortalized MSC lines were created and used to study the role of FGFRs in osteoblast and adipocyte differentiation.•MSCs express FGFR1-3 and FGFRL1. Their expression profile is altered during differentiation.•FGFR2 and FGFRL1 mRNAs expression increased in osteoblastic and FGFR1 and FGFRL1 in adipocyte lineage upon differentiation.•Silencing FGFR2 inhibited osteoblastic and FGFR1 adipocytic differentiation, respectively.•FGFR1 or FGFR2 knockdown altered FGFRL1 expression suggesting that it has a novel role in MSC differentiation.