scholarly journals RECENT RESEARCH ON THE GROWTH PLATE: Advances in fibroblast growth factor signaling in growth plate development and disorders

2014 ◽  
Vol 53 (1) ◽  
pp. T11-T34 ◽  
Author(s):  
Yangli Xie ◽  
Siru Zhou ◽  
Hangang Chen ◽  
Xiaolan Du ◽  
Lin Chen
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Molecular Mechanisms ◽  
Skeletal Development ◽  
Vital Role ◽  
Growth Factor Signaling ◽  
Missense Mutations ◽  
Fibroblast Growth

Skeletons are formed through two distinct developmental actions, intramembranous ossification and endochondral ossification. During embryonic development, most bone is formed by endochondral ossification. The growth plate is the developmental center for endochondral ossification. Multiple signaling pathways participate in the regulation of endochondral ossification. Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling has been found to play a vital role in the development and maintenance of growth plates. Missense mutations inFGFsandFGFRscan cause multiple genetic skeletal diseases with disordered endochondral ossification. Clarifying the molecular mechanisms of FGFs/FGFRs signaling in skeletal development and genetic skeletal diseases will have implications for the development of therapies for FGF-signaling-related skeletal dysplasias and growth plate injuries. In this review, we summarize the recent advances in elucidating the role of FGFs/FGFRs signaling in growth plate development, genetic skeletal disorders, and the promising therapies for those genetic skeletal diseases resulting from FGFs/FGFRs dysfunction. Finally, we also examine the potential important research in this field in the future.

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

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0241281
Author(s):  
Xiaoyue Zhang ◽  
Mengjia Weng ◽  
Zhenqi Chen
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Endochondral Ossification ◽  
Early Stage ◽  
Growth Factor Signaling ◽  
Fibroblast Growth ◽  
Mtor Inhibition ◽  
Early Differentiation ◽  
Important Regulator ◽  
Gsk 3Β

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.

scholarly journals Targeting fibroblast growth factor receptors to combat aggressive ependymoma

2021 ◽  
Author(s):  
Daniela Lötsch ◽  
Dominik Kirchhofer ◽  
Bernhard Englinger ◽  
Li Jiang ◽  
Konstantin Okonechnikov ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Growth Factor Receptors ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Cell Models ◽  
Fibroblast Growth Factor Receptors

AbstractEpendymomas (EPN) are central nervous system tumors comprising both aggressive and more benign molecular subtypes. However, therapy of the high-risk subtypes posterior fossa group A (PF-A) and supratentorial RELA-fusion positive (ST-RELA) is limited to gross total resection and radiotherapy, as effective systemic treatment concepts are still lacking. We have recently described fibroblast growth factor receptors 1 and 3 (FGFR1/FGFR3) as oncogenic drivers of EPN. However, the underlying molecular mechanisms and their potential as therapeutic targets have not yet been investigated in detail. Making use of transcriptomic data across 467 EPN tissues, we found that FGFR1 and FGFR3 were both widely expressed across all molecular groups. FGFR3 mRNA levels were enriched in ST-RELA showing the highest expression among EPN as well as other brain tumors. We further identified high expression levels of fibroblast growth factor 1 and 2 (FGF1, FGF2) across all EPN subtypes while FGF9 was elevated in ST-EPN. Interrogation of our EPN single-cell RNA-sequencing data revealed that FGFR3 was further enriched in cycling and progenitor-like cell populations. Corroboratively, we found FGFR3 to be predominantly expressed in radial glia cells in both mouse embryonal and human brain datasets. Moreover, we detected alternative splicing of the FGFR1/3-IIIc variant, which is known to enhance ligand affinity and FGFR signaling. Dominant-negative interruption of FGFR1/3 activation in PF-A and ST-RELA cell models demonstrated inhibition of key oncogenic pathways leading to reduced cell growth and stem cell characteristics. To explore the feasibility of therapeutically targeting FGFR, we tested a panel of FGFR inhibitors in 12 patient-derived EPN cell models revealing sensitivity in the low-micromolar to nano-molar range. Finally, we gain the first clinical evidence for the activity of the FGFR inhibitor nintedanib in the treatment of a patient with recurrent ST-RELA. Together, these preclinical and clinical data suggest FGFR inhibition as a novel and feasible approach to combat aggressive EPN.

scholarly journals Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma

Hepatology ◽  
2008 ◽  
Vol 47 (4) ◽  
pp. 1211-1222 ◽  
Author(s):  
Jin-Ping Lai ◽  
Dalbir S. Sandhu ◽  
Chunrong Yu ◽  
Tao Han ◽  
Catherine D. Moser ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Signaling ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Signaling

scholarly journals BASIC FIBROBLAST GROWTH FACTOR AND ADIPONECTIN IN ADOLESCENCE WITH JUVENILE IDIOPATHIC ARTHRITIS TREATED WITH METHOTREXATE

2020 ◽  
Vol 4 ◽  
pp. 70-76
Author(s):  
Liudmyla Parkhomenko ◽  
Larysa Strashok ◽  
Olga Pavlova
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Molecular Mechanisms ◽  
Fibroblast Growth ◽  
Cellular Mechanisms ◽  
Reactive Protein ◽  
Study Results ◽  
Methotrexate Dose

Methotrexate has been applied clinically for juvenile idiopathic arthritis (JIA) treatment for decades. It is recommended for use globally, according all modern guidelines. Despite the fact that fibrosis molecular mechanisms as well as methotrexate (MTX) elimination and fibrosis indexes were studied a lot there is still not enough information for adolescence. Adiponectin, fibroblast growth factor and fibrosis indexes in adolescents with JIA treated with methotrexate were studied in this work. The aim was to study dynamics of molecular-cellular mechanisms activation of fibrotic processes development in the liver in adolescents with juvenile idiopathic arthritis treated with methotrexate. Materials and methods: A total of 68 children with juvenile idiopathic arthritis, were enrolled in the study. 25 boys (36.8 %) and 43 girls (63.2 %) were examined. Children were divided into three groups in accordance with the methotrexate dose. The following data were analyzed: ESR (mm/hour), C-reactive protein (mg/l), Hemolytic activity (CU), circulating immune complexes, (g/l), ALT (U/l), AST (U/l), Adiponectin (mcg/ml), BFGF (pg/ml), APRI index, FIB-4 Score. Results: According to our results when patients start using MTX they have significantly positive effect. Therefore, when analyzing all parameters liver pathologies may occur before MTX use. When MTX used, its proinflammation and antifibrotic effects lead to normalization of all organs and systems, as well as joints and liver. Also, long-term MTX use can lead to adverse effects. Conclusions: So, it is important to control possible liver disorders in adolescence treated with MTX. According to our study results we find out that there are decreasing of liver damage parameters in patients which started using MTX.

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