Basic fibroblast growth factor increases IFT88 expression in chondrocytes

Zhan,Daolu; Xiang,Wei; Guo,Fengjing; Ma,Yuanzheng

doi:10.3892/mmr.2017.7449

Basic fibroblast growth factor increases IFT88 expression in chondrocytes

Authors:
- Daolu Zhan
- Wei Xiang
- Fengjing Guo
- Yuanzheng Ma
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Affiliations: Graduate School, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: September 8, 2017 https://doi.org/10.3892/mmr.2017.7449
Pages: 6590-6599
Copyright: © Zhan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intraflagellar transport protein 88 (IFT88) is protein crucial for the assembly and maintenance of primary cilia in chondrocytes. Primary cilia regulate mechanical and chemical signals in chondrocytes; however, the effects of cytokines on IFT88 expression and cilia formation and maintenance remain to be elucidated. Therefore, the role of basic fibroblast growth factor (bFGF) on IFT88 expression were examined in theATDC5 murine chondrocytic line, in order to investigate the signaling pathways involved in this process. bFGF treatment upregulated IFT88 expression in a dose‑ and time‑dependent manner in ATDC5 cells. The effects of bFGF on IFT88 protein expression were suppressed in the presence of the extracellular signal‑regulated protein kinase (ERK) inhibitor PD0325901 and the FGF receptor inhibitor BGJ398. In addition, treatment with IFT88‑trageting small interfering (si)RNA downregulated the protein expression of IFT88 and ERK, thus suggesting that the ERK signaling pathway may be involved in the regulation of IFT88 expression in ATDC5 cells. bFGF treatment increased the number of ciliated ATDC5 cells and primary cultured chondrocytes. Downregulation of IFT88 expression by PD0325901, BGJ398, or IFT88‑targeting siRNA was revealed to reduce the number of ciliated cells. bFGF also upregulated the mRNA and protein expression of IFT88 in primary cultured chondrocytes. In conclusion, the findings of the present study suggested that bFGF may enhance the expression of IFT88, and promote primary cilia development, through the mitogen‑activated protein kinase/ERK‑mediated pathway in chondrocytes.

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1	Seeley ES and Nachury MV: The perennial organelle: Assembly and disassembly of the primary cilium. J Cell Sci. 123:511–518. 2010. View Article : Google Scholar : PubMed/NCBI
2	Kim S and Dynlacht BD: Assembling a primary cilium. Curr Opin Cell Biol. 25:506–511. 2013. View Article : Google Scholar : PubMed/NCBI
3	Satir P and Christensen ST: Overview of structure and function of mammalian cilia. Annu Rev Physiol. 69:377–400. 2007. View Article : Google Scholar : PubMed/NCBI
4	Enuka Y, Hanukoglu I, Edelheit O, Vaknine H and Hanukoglu A: Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways. Histochem Cell Biol. 137:339–353. 2012. View Article : Google Scholar : PubMed/NCBI
5	Tobin JL and Beales PL: The nonmotile ciliopathies. Genet Med. 11:386–402. 2009. View Article : Google Scholar : PubMed/NCBI
6	Hoey DA, Tormey S, Ramcharan S, O'Brien FJ and Jacobs CR: Primary cilia-mediated mechanotransduction in human mesenchymal stem cells. Stem Cells. 30:2561–2570. 2012. View Article : Google Scholar : PubMed/NCBI
7	Ishikawa H and Marshall WF: Ciliogenesis: Building the cell's antenna. Nat Rev Mol Cell Biol. 12:222–234. 2011. View Article : Google Scholar : PubMed/NCBI
8	Muhammad H, Rais Y, Miosge N and Ornan EM: The primary cilium as a dual sensor of mechanochemical signals in chondrocytes. Cell Mol Life Sci. 69:2101–2107. 2012. View Article : Google Scholar : PubMed/NCBI
9	Rosenbaum JL and Witman GB: Intraflagellar transport. Nat Rev Mol Cell Biol. 3:813–825. 2002. View Article : Google Scholar : PubMed/NCBI
10	Mizuno N, Taschner M, Engel BD and Lorentzen E: Structural studies of ciliary components. J Mol Biol. 422:163–180. 2012. View Article : Google Scholar : PubMed/NCBI
11	Sung CH and Leroux MR: The roles of evolutionarily conserved functional modules in cilia-related trafficking. Nat Cell Biol. 15:1389–1397. 2013. View Article : Google Scholar
12	Pazour GJ, Baker SA, Deane JA, Cole DG, Dickert BL, Rosenbaum JL, Witman GB and Besharse JC: The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J Cell Biol. 157:103–113. 2002. View Article : Google Scholar : PubMed/NCBI
13	Pazour GJ, Dickert BL, Vucica Y, Seeley ES, Rosenbaum JL, Witman GB and Cole DG: Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol. 151:709–718. 2000. View Article : Google Scholar : PubMed/NCBI
14	Friedl A, Chang Z, Tierney A and Rapraeger AC: Differential binding of fibroblast growth factor-2 and −7 to basement membrane heparin sulfate: Comparison of normal and abnormal human tissues. Am J Pathol. 150:1443–1455. 1997.PubMed/NCBI
15	Okada-Ban M, Thiery JP and Jouanneau J: Fibroblast growth factor-2. Int J Biochem Cell Biol. 32:263–267. 2000. View Article : Google Scholar : PubMed/NCBI
16	Song H, Kwon K, Lim S, Kang SM, Ko YG, Xu Z, Chung JH, Kim BS, Lee H, Joung B, et al: Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Mol Cells. 19:402–407. 2005.PubMed/NCBI
17	Ng EW and Adamis AP: Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can J Ophthalmol. 40:352–368. 2005. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	McGlashan SR, Cluett EC, Jensen CG and Poole CA: Primary cilia in osteoarthritic chondrocytes: From chondrons to clusters. Dev Dyn. 237:2013–2020. 2008. View Article : Google Scholar : PubMed/NCBI
20	Wann AK, Zuo N, Haycraft CJ, Jensen CG, Poole CA, McGlashan SR and Knight MM: Primary cilia mediate mechanotransduction through control of ATP-induced Ca2⁺ signaling in compressed chondrocytes. FASEB J. 26:1663–1671. 2012. View Article : Google Scholar : PubMed/NCBI
21	Chang CF, Ramaswamy G and Serra R: Depletion of primary cilia in articular chondrocytes result in reduced Gli3 repressor to activator ratio, increased Hedgehog signaling, and symptoms of early osteoarthritis. Osteoarthritis Cartilage. 20:152–161. 2012. View Article : Google Scholar : PubMed/NCBI
22	Li X, Ellman MB, Kroin JS, Chen D, Yan D, Mikecz K, Ranjan KC, Xiao G, Stein GS, Kim SG, et al: Species-specific biological effects of FGF-2 in articular cartilage: Implication for distinct roles within the FGF receptor family. J Cell Biochem. 113:2532–2542. 2012. View Article : Google Scholar : PubMed/NCBI
23	Chia SL, Sawaji Y, Burleigh A, McLean C, Inglis J, Saklatvala J and Vincent T: Fibroblast growth factor 2 is an intrinsic chondroprotective agent that suppresses ADAMTS-5 and delays cartilage degradation in murine osteoarthritis. Arthritis Rheum. 60:2019–2027. 2009. View Article : Google Scholar : PubMed/NCBI
24	Yan D, Chen D, Cool SM, Van Wijnen AJ, Mikecz K, Murphy G and Im HJ: Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes. Arthritis Res Ther. 13:R1302011. View Article : Google Scholar : PubMed/NCBI
25	Yan D, Chen D and Im HJ: Fibroblast growth factor-2 promotes catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 axis that coordinates with the PKCδ pathway in human articular chondrocytes. J Cell Biochem. 113:2856–2865. 2012. View Article : Google Scholar : PubMed/NCBI
26	Pazour GJ and Witman GB: The vertebrate primary cilium is a sensory organelle. Curr Opin Cell Biol. 15:105–110. 2003. View Article : Google Scholar : PubMed/NCBI
27	Bloodgood RA: Sensory reception is an attribute of both primary cilia and motile cilia. J Cell Sci. 123:505–509. 2010. View Article : Google Scholar : PubMed/NCBI
28	Xiang W, Jiang T, Guo F, Gong C, Yang K, Wu Y, Huang X, Cheng W and Xu K: Hedgehog pathway inhibitor-4 suppresses malignant properties of chondrosarcoma cells by disturbing tumor ciliogenesis. Oncol Rep. 32:1622–1630. 2014. View Article : Google Scholar : PubMed/NCBI