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Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis

David Davidson, Antoine Blanc, Dominic Filion, Huifen Wang, Paul Plut, Gerald Pfeffer, Michael D. Buschmann and Janet E. Henderson

Article (2005)

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Signaling by fibroblast growth factor (FGF) 18 and FGF receptor 3 (FGFR3) have been shown to regulate proliferation, differentiation, and matrix production of articular and growth plate chondrocytes in vivo and in vitro. Notably, the congenital absence of either FGF18 or FGFR3 resulted in similar expansion of the growth plates of fetal mice and the addition of FGF18 to human articular chondrocytes in culture enhanced proliferation and matrix production. Based on these and other experiments it has been proposed that FGF18 signals through FGFR3 to promote cartilage production by chondrocytes. Its role in chondrogenesis remains to be defined. In the current work we used the limb buds of FGFR3+/+ and FGFR3–/– embryonic mice as a source of mesenchymal cells to determine how FGF18 signaling affects chondrogenesis. Confocal laser-scanning microscopy demonstrated impaired cartilage nodule formation in the FGFR3–/– cultures. Potential contributing factors to the phenotype were identified as impaired mitogenic response to FGF18, decreased production of type II collagen and proteoglycan in response to FGF18 stimulation, impaired interactions with the extracellular matrix resulting from altered integrin receptor expression, and altered expression of FGFR1 and FGFR2. The data identified FGF18 as a selective ligand for FGFR3 in limb bud mesenchymal cells, which suppressed proliferation and promoted their differentiation and production of cartilage matrix. This work, thus, identifies FGF18 and FGFR3 as potential molecular targets for intervention in tissue engineering aimed at cartilage repair and regeneration of damaged cartilage.

Subjects: 1800 Chemical engineering > 1800 Chemical engineering
1800 Chemical engineering > 1802 Biochemical engineering
Department: Department of Chemical Engineering
Funders: CRSNG / NSERC, Arthritis Society of Canada (TAS), Canadian Arthritis Network Centres of Excellence, Canadian Institutes of Health and Research
PolyPublie URL: https://publications.polymtl.ca/24230/
Journal Title: Journal of Biological Chemistry (vol. 280, no. 21)
Publisher: Elsevier
DOI: 10.1074/jbc.m410148200
Official URL: https://doi.org/10.1074/jbc.m410148200
Date Deposited: 18 Apr 2023 15:18
Last Modified: 25 Jun 2024 12:26
Cite in APA 7: Davidson, D., Blanc, A., Filion, D., Wang, H., Plut, P., Pfeffer, G., Buschmann, M. D., & Henderson, J. E. (2005). Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. Journal of Biological Chemistry, 280(21), 20509-20515. https://doi.org/10.1074/jbc.m410148200


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