Open AccessCatabolic effects of FGF‐1 on chondrocytes and its possible role in osteoarthritis
Author(s) -
ElSeoudi Abdellatif,
Abd El Kader Tarek,
Nishida Takashi,
Eguchi Takanori,
Aoyama Eriko,
Takigawa Masaharu,
Kubota Satoshi
Publication year - 2017
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-017-0384-8
Subject(s) - fibroblast growth factor , cartilage , extracellular matrix , microbiology and biotechnology , osteoarthritis , reporter gene , psychological repression , matrix metalloproteinase , catabolism , growth factor , fibroblast , gene expression , in vitro , chemistry , gene , biology , medicine , endocrinology , pathology , anatomy , genetics , receptor , alternative medicine , metabolism
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.