Abstract
ObjectivesFibroblast Growth Factor 23 (FGF23) is well documented as a crucial player in the systemic regulation of phosphate homeostasis. Moreover, loss-of-function experiments have revealed that FGF23 also has a phosphate-independent and local impact on skeletogenesis. Here, we used ATDC5 cell line to investigate the expression of FGF23 and the role it may play locally during the differentiation of these cells.MethodsATDC5 cells were differentiated in the presence of insulin, and treated with recombinant FGF23 (rFGF23), inorganic phosphate (Pi) and/or PD173074, an inhibitor of FGF receptors (FGFRs). The mRNA expressions of FGF23, FGFRs and markers of hypertophy, Col X and MMP13, were determined by qPCR analysis and FGF23 production was assessed by ELISA. FGFR activation was determined by immunoprecipitation and immunoblotting.ResultsFGF23 mRNA expression and production were increased during ATDC5 differentiation. At D28 in particular, rFGF23 stimulation increased hypertrophic markers expression, as Col X and MMP13, and mineralization. A synergic effect of Pi and rFGF23 stimulation was observed on these markers and on the mineralization process. The use of PD173074, a pan-FGFR inhibitor, decreased terminal differentiation of ATDC5 by preventing rFGF23 pro-hypertrophic effects.ConclusionsAltogether, our results provide evidence that FGF23 plays an important role during differentiation of ATDC5 cell line, by promoting both hypertrophy and mineralization.
Highlights
Chondrogenesis is a tightly regulated process that results in the formation of the cartilage anlage and leads to endochondral ossification during skeletal development
Our results provide evidence that Fibroblast Growth Factor 23 (FGF23) plays an important role during differentiation of ATDC5 cell line, by promoting both hypertrophy and mineralization
If canonical Fibroblast Growth Factors (FGFs) signalling via high-affinity FGF receptors (FGFRs) receptors (FGFR1-4) exhibit important roles in all cells types, they are best known for the critical role they play in the development of the skeletal system [3]
Summary
Chondrogenesis is a tightly regulated process that results in the formation of the cartilage anlage and leads to endochondral ossification during skeletal development. Tremendous work over the past decades has revealed the role of various signaling molecules and their crosstalk in the orderly process of endochondral ossification that takes place within the growth plate. A few years later, work from Sitara et al suggested a local role of FGF23 in the skeletal system. They demonstrated that FGF23-/- mice display both a decreased in the number of hypertrophic chondrocytes and a mineralization defect in their growth plate in a phosphate-independent manner [5,6]. Together with the expression of FGF23 recently reported in hypertrophic chondrocytes [7], this was highly suggestive of a local role of FGF23 in endochondral ossification
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
