Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.

Fibroblast growth factor signaling is essential for mammalian bone morphogenesis and growth, involving membranous ossification and endochondral ossification. FGF9 has been shown to be an important regulator of endochondral ossification; however, its role in the early differentiation of chondrocytes...

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Main Authors: Xiaoyue Zhang, Mengjia Weng, Zhenqi Chen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0241281
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author Xiaoyue Zhang
Mengjia Weng
Zhenqi Chen
author_facet Xiaoyue Zhang
Mengjia Weng
Zhenqi Chen
author_sort Xiaoyue Zhang
collection DOAJ
description Fibroblast growth factor signaling is essential for mammalian bone morphogenesis and growth, involving membranous ossification and endochondral ossification. FGF9 has been shown to be an important regulator of endochondral ossification; however, its role in the early differentiation of chondrocytes remains unknown. Therefore, in this study, we aimed to determine the role of FGF9 in the early differentiation of chondrogenesis. We found an increase in FGF9 expression during proliferating chondrocyte hypertrophy in the mouse growth plate. Silencing of FGF9 promotes the growth of ATDC5 cells and promotes insulin-induced differentiation of ATDC5 chondrocytes, which is due to increased cartilage matrix formation and type II collagen (col2a1) and X (col10a1), Acan, Ihh, Mmp13 gene expression. Then, we evaluated the effects of AKT, GSK-3β, and mTOR. Inhibition of FGF9 significantly inhibits phosphorylation of AKT and GSK-3β, but does not affected the activation of mTOR. Furthermore, phosphorylation of inhibited AKT and GSK-3β was compensated using the AKT activator SC79, and differentiation of ATDC5 cells was inhibited. In conclusion, our results indicate that FGF9 acts as an important regulator of early chondrogenesis partly through the AKT/GSK-3β pathway.
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spelling doaj.art-3b11303a36bb420c89c94c88abaf66b92022-12-21T19:24:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e024128110.1371/journal.pone.0241281Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.Xiaoyue ZhangMengjia WengZhenqi ChenFibroblast growth factor signaling is essential for mammalian bone morphogenesis and growth, involving membranous ossification and endochondral ossification. FGF9 has been shown to be an important regulator of endochondral ossification; however, its role in the early differentiation of chondrocytes remains unknown. Therefore, in this study, we aimed to determine the role of FGF9 in the early differentiation of chondrogenesis. We found an increase in FGF9 expression during proliferating chondrocyte hypertrophy in the mouse growth plate. Silencing of FGF9 promotes the growth of ATDC5 cells and promotes insulin-induced differentiation of ATDC5 chondrocytes, which is due to increased cartilage matrix formation and type II collagen (col2a1) and X (col10a1), Acan, Ihh, Mmp13 gene expression. Then, we evaluated the effects of AKT, GSK-3β, and mTOR. Inhibition of FGF9 significantly inhibits phosphorylation of AKT and GSK-3β, but does not affected the activation of mTOR. Furthermore, phosphorylation of inhibited AKT and GSK-3β was compensated using the AKT activator SC79, and differentiation of ATDC5 cells was inhibited. In conclusion, our results indicate that FGF9 acts as an important regulator of early chondrogenesis partly through the AKT/GSK-3β pathway.https://doi.org/10.1371/journal.pone.0241281
spellingShingle Xiaoyue Zhang
Mengjia Weng
Zhenqi Chen
Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.
PLoS ONE
title Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.
title_full Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.
title_fullStr Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.
title_full_unstemmed Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.
title_short Fibroblast Growth Factor 9 (FGF9) negatively regulates the early stage of chondrogenic differentiation.
title_sort fibroblast growth factor 9 fgf9 negatively regulates the early stage of chondrogenic differentiation
url https://doi.org/10.1371/journal.pone.0241281
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AT mengjiaweng fibroblastgrowthfactor9fgf9negativelyregulatestheearlystageofchondrogenicdifferentiation
AT zhenqichen fibroblastgrowthfactor9fgf9negativelyregulatestheearlystageofchondrogenicdifferentiation