Abstract
Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model. Treatment of human chondrocytic cells with FGF-1 resulted in marked repression of genes for cartilaginous extracellular matrix components, whereas it strongly induced matrix metalloproteinase 13 (MMP-13), representing its catabolic effects on cartilage. Interestingly, expression of the CCN2 gene was dramatically repressed by FGF-1, which repression eventually caused the reduced production of CCN2 protein from the chondrocytic cells. The results of a reporter gene assay revealed that this repression could be ascribed, at least in part, to transcriptional regulation. In contrast, the gene expression of FGF-1 was enhanced by exogenous FGF-1, indicating a positive feedback system in these cells. Of note, induction of FGF-1 was observed in the articular cartilage of a rat OA model. These results collectively indicate a pathological role of FGF-1 in OA development, which includes an insufficient cartilage regeneration response caused by CCN2 down regulation.
| Original language | English |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Journal of Cell Communication and Signaling |
| DOIs | |
| Publication status | Accepted/In press - Mar 25 2017 |
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Keywords
- Cartilage
- CCN2
- Chondrocytes
- FGF-1
- Osteoarthritis
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis. / El-Seoudi, Abdellatif; El Kader, Tarek Abd; Nishida, Takashi; Eguchi, Takanori; Aoyama, Eriko; Takigawa, Masaharu; Kubota, Satoshi.
In: Journal of Cell Communication and Signaling, 25.03.2017, p. 1-9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis
AU - El-Seoudi, Abdellatif
AU - El Kader, Tarek Abd
AU - Nishida, Takashi
AU - Eguchi, Takanori
AU - Aoyama, Eriko
AU - Takigawa, Masaharu
AU - Kubota, Satoshi
PY - 2017/3/25
Y1 - 2017/3/25
N2 - Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model. Treatment of human chondrocytic cells with FGF-1 resulted in marked repression of genes for cartilaginous extracellular matrix components, whereas it strongly induced matrix metalloproteinase 13 (MMP-13), representing its catabolic effects on cartilage. Interestingly, expression of the CCN2 gene was dramatically repressed by FGF-1, which repression eventually caused the reduced production of CCN2 protein from the chondrocytic cells. The results of a reporter gene assay revealed that this repression could be ascribed, at least in part, to transcriptional regulation. In contrast, the gene expression of FGF-1 was enhanced by exogenous FGF-1, indicating a positive feedback system in these cells. Of note, induction of FGF-1 was observed in the articular cartilage of a rat OA model. These results collectively indicate a pathological role of FGF-1 in OA development, which includes an insufficient cartilage regeneration response caused by CCN2 down regulation.
AB - Fibroblast growth factor 1 (FGF-1) is a classical member of the FGF family and is produced by chondrocytes cultured from osteoarthritic patients. Also, this growth factor was shown to bind to CCN family protein 2 (CCN2), which regenerates damaged articular cartilage and counteracts osteoarthritis (OA) in an animal model. However, the pathophysiological role of FGF-1 in cartilage has not been well investigated. In this study, we evaluated the effects of FGF-1 in vitro and its production in vivo by use of an OA model. Treatment of human chondrocytic cells with FGF-1 resulted in marked repression of genes for cartilaginous extracellular matrix components, whereas it strongly induced matrix metalloproteinase 13 (MMP-13), representing its catabolic effects on cartilage. Interestingly, expression of the CCN2 gene was dramatically repressed by FGF-1, which repression eventually caused the reduced production of CCN2 protein from the chondrocytic cells. The results of a reporter gene assay revealed that this repression could be ascribed, at least in part, to transcriptional regulation. In contrast, the gene expression of FGF-1 was enhanced by exogenous FGF-1, indicating a positive feedback system in these cells. Of note, induction of FGF-1 was observed in the articular cartilage of a rat OA model. These results collectively indicate a pathological role of FGF-1 in OA development, which includes an insufficient cartilage regeneration response caused by CCN2 down regulation.
KW - Cartilage
KW - CCN2
KW - Chondrocytes
KW - FGF-1
KW - Osteoarthritis
UR - http://www.scopus.com/inward/record.url?scp=85016189277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016189277&partnerID=8YFLogxK
U2 - 10.1007/s12079-017-0384-8
DO - 10.1007/s12079-017-0384-8
M3 - Article
AN - SCOPUS:85016189277
SP - 1
EP - 9
JO - Journal of Cell Communication and Signaling
JF - Journal of Cell Communication and Signaling
SN - 1873-9601
ER -