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.
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Acknowledgments
The authors thank Drs. Takako Hattori, Danilo Janune, and Chikako Hara for their helpful support in experiments, as well as Ms. Yoshiko Miyake for her secretarial assistance. This study was supported by grants from the program Grants-in-aid for Scientific Research (B) [#15H0514 to M.T.], and (C) [#25462886 to S.K.] from the Japan Society for the Promotion of Science.
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El-Seoudi, A., Abd El Kader, T., Nishida, T. et al. Catabolic effects of FGF-1 on chondrocytes and its possible role in osteoarthritis. J. Cell Commun. Signal. 11, 255–263 (2017). https://doi.org/10.1007/s12079-017-0384-8
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DOI: https://doi.org/10.1007/s12079-017-0384-8