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Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis.
J Biol Chem 2005; 280(21):20509-15JB

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Centre for Bone and Periodontal Research, McGill University, Montreal H3A 1A4, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15781473

Citation

Davidson, David, et al. "Fibroblast Growth Factor (FGF) 18 Signals Through FGF Receptor 3 to Promote Chondrogenesis." The Journal of Biological Chemistry, vol. 280, no. 21, 2005, pp. 20509-15.
Davidson D, Blanc A, Filion D, et al. Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem. 2005;280(21):20509-15.
Davidson, D., Blanc, A., Filion, D., Wang, H., Plut, P., Pfeffer, G., ... Henderson, J. E. (2005). Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. The Journal of Biological Chemistry, 280(21), pp. 20509-15.
Davidson D, et al. Fibroblast Growth Factor (FGF) 18 Signals Through FGF Receptor 3 to Promote Chondrogenesis. J Biol Chem. 2005 May 27;280(21):20509-15. PubMed PMID: 15781473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. AU - Davidson,David, AU - Blanc,Antoine, AU - Filion,Dominic, AU - Wang,Huifen, AU - Plut,Paul, AU - Pfeffer,Gerald, AU - Buschmann,Michael D, AU - Henderson,Janet E, Y1 - 2005/03/21/ PY - 2005/3/23/pubmed PY - 2005/8/16/medline PY - 2005/3/23/entrez SP - 20509 EP - 15 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 280 IS - 21 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15781473/Fibroblast_growth_factor__FGF__18_signals_through_FGF_receptor_3_to_promote_chondrogenesis_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15781473 DB - PRIME DP - Unbound Medicine ER -