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Article

Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression

  • Authors:
    • Long-Qiang Zhang
    • Guang-Zong Zhao
    • Xiao-Yan Xu
    • Jun Fang
    • Jing-Ming Chen
    • Ji-Wen Li
    • Xue-Jian Gao
    • Li-Juan Hao
    • Yun-Zhen Chen
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China, Department of Oncology, Qingzhou Hospital of Traditional Chinese Medicine, Qingzhou, Shandong 262500, P.R. China, Department of Orthopedics, The 89th Hospital of PLA, Weifang, Shandong 261021, P.R. China, Department of Urologic Surgery, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China
  • Pages: 1074-1080
    |
    Published online on: February 26, 2015
       https://doi.org/10.3892/ijmm.2015.2114
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Abstract

Chondrocytes play a critical role in the repair process of osteoarthritis, which is also known as degenerative arthritis. Integrins, as the key family of cell surface receptors, are responsible for the regulation of chondrocyte proliferation, differentiation, survival and apoptosis through the recruitment and activation of downstream adaptor proteins. Moreover, G-protein‑coupled receptor kinase interacting protein-1 (GIT1) exerts its effects on cell proliferation and migration through interaction with various cytokines. It has been previously suggested that GIT1 acts as a vital protein downstream of the integrin-mediated pathway. In the present study, we investigated the effects of integrin-β1 on cell proliferation and apoptosis, as well as the underlying mechanisms in chondrocytes in vitro. Following transfection with a vector expressing integrin-β1, our results revealed that the overexpression of integrin-β1 enhanced GIT1 expression, whereas the knockdown of integrin-β1 by siRNA suppressed GIT1 expression. However, no significant effect was observed on integrin-β1 expression following the enforced overexpression of GIT1, which suggests that GIT1 is localized downstream of integrin-β1. In other words, integrin-β1 regulates the expression of GIT1. Furthermore, this study demonstrated that integrin-β1 and GIT1 increased the expression levels of aggrecan and type II collagen, thus promoting chondrocyte proliferation; however, they inhibited chondrocyte apoptosis. Taken together, our data demonstrate that integrin-β1 plays a vital role in chondrocyte proliferation, differentiation and apoptosis. GIT1 exerts effects similar to those of integrin-β1 and is a downstream target of integrin-β1.
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1 

Fernandes AM, Herlofsen SR, Karlsen TA, Küchler AM, Fløisand Y and Brinchmann JE: Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage. PLoS One. 8:e629942013. View Article : Google Scholar : PubMed/NCBI

2 

Dreier R: Hypertrophic differentiation of chondrocytes in osteoarthritis: the developmental aspect of degenerative joint disorders. Arthritis Res Ther. 12:2162010. View Article : Google Scholar : PubMed/NCBI

3 

Tanaka Y, Ogasawara T, Asawa Y, Yamaoka H, Nishizawa S, Mori Y, Takato T and Hoshi K: Growth factor contents of autologous human sera prepared by different production methods and their biological effects on chondrocytes. Cell Biol Int. 32:505–514. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Lowell CA and Mayadas TN: Overview: studying integrins in vivo. Methods Mol Biol. 757:369–397. 2012. View Article : Google Scholar

5 

Brakebusch C, Bouvard D, Stanchi F, Sakai T and Fassler R: Integrins in invasive growth. J Clin Invest. 109:999–1006. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Spiteri C, Raizman I, Pilliar RM and Kandel RA: Matrix accumulation by articular chondrocytes during mechanical stimulation is influenced by integrin-mediated cell spreading. J Biomed Mater Res A. 94:122–129. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Premont RT, Claing A, Vitale N, Freeman JL, Pitcher JA, Patton WA, Moss J, Vaughan M and Lefkowitz RJ: beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Proc Natl Acad Sci USA. 95:14082–14087. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Claing A, Chen W, Miller WE, Vitale N, Moss J, Premont RT and Lefkowitz RJ: beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic receptor endocytosis. J Biol Chem. 276:42509–42513. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Hsu RM, Tsai MH, Hsieh YJ, Lyu PC and Yu JS: Identification of MYO18A as a novel interacting partner of the PAK2/betaPIX/GIT1 complex and its potential function in modulating epithelial cell migration. Mol Biol Cell. 21:287–301. 2010. View Article : Google Scholar :

10 

Gavina M, Za L, Molteni R, Pardi R and de Curtis I: The GIT-PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells. Biol Cell. 102:231–244. 2010. View Article : Google Scholar

11 

Menon P, Yin G, Smolock EM, Zuscik MJ, Yan C and Berk BC: GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass. J Cell Physiol. 225:777–785. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Ren Y, Yu L, Fan J, Rui Z, Hua Z, Zhang Z, Zhang N and Yin G: Phosphorylation of GIT1 tyrosine 321 is required for association with FAK at focal adhesions and for PDGF-activated migration of osteoblasts. Mol Cell Biochem. 365:109–118. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Liu J, Zeng L, Kennedy RM, Gruenig NM and Childs SJ: βPix plays a dual role in cerebral vascular stability and angiogenesis, and interacts with integrin αvβ8. Dev Biol. 363:95–105. 2012. View Article : Google Scholar

14 

Sato H, Suzuki-Inoue K, Inoue O and Ozaki Y: Regulation of adaptor protein GIT1 in platelets, leading to the interaction between GIT1 and integrin alpha(IIb)beta3. Biochem Biophys Res Commun. 368:157–161. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Loeser RF, Sadiev S, Tan L and Goldring MB: Integrin expression by primary and immortalized human chondrocytes: evidence of a differential role for alpha1beta1 and alpha2beta1 integrins in mediating chondrocyte adhesion to types II and VI collagen. Osteoarthritis Cartilage. 8:96–105. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Gigout A, Jolicoeur M, Nelea M, Raynal N, Farndale R and Buschmann MD: Chondrocyte aggregation in suspension culture is GFOGER-GPP- and beta1 integrin-dependent. J Biol Chem. 283:31522–31530. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Ren K, Ma Y, Huang Y, Liang W, Liu F, Wang Q, Cui W, Liu Z, Yin G and Fan W: Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1. Braz J Med Biol Res. 44:1231–1242. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Gohlke H, Schmitz B, Sommerfeld A, Reinehr R and Haussinger D: α5 β1-integrins are sensors for tauroursodeoxycholic acid in hepatocytes. Hepatology. 57:1117–1129. 2013. View Article : Google Scholar

19 

Kim SH, Turnbull J and Guimond S: Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol. 209:139–151. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Schagemann JC1, Kurz H, Casper ME, Stone JS, Dadsetan M, Yu-Long S, Mrosek EH, Fitzsimmons JS, O’Driscoll SW and Reinholz GG: The effect of scaffold composition on the early structural characteristics of chondrocytes and expression of adhesion molecules. Biomaterials. 31:2798–2805. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Wang G, Woods A, Sabari S, Pagnotta L, Stanton LA and Beier F: RhoA/ROCK signaling suppresses hypertrophic chondrocyte differentiation. J Biol Chem. 279:13205–13214. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Enomoto-Iwamoto M, Iwamoto M, Nakashima K, Mukudai Y, Boettiger D, Pacifici M, Kurisu K and Suzuki F: Involvement of alpha5beta1 integrin in matrix interactions and proliferation of chondrocytes. J Bone Miner Res. 12:1124–1132. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Cao L, Lee V, Adams ME, Kiani C, Zhang Y, Hu W and Yang BB: beta-Integrin-collagen interaction reduces chondrocyte apoptosis. Matrix Biol. 18:343–355. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Lee DY, Li YS, Chang SF, Zhou J, Ho HM, Chiu JJ and Chien S: Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphati-dylinositol 3-kinase and the Akt/mTOR/p70S6K pathway. J Biol Chem. 285:30–42. 2010. View Article : Google Scholar :

25 

Poole AR, Nelson F, Dahlberg L, et al: Proteolysis of the collagen fibril in osteoarthritis. Biochem Soc Symp. 70:115–123. 2003.PubMed/NCBI

26 

Henrotin Y, Addison S, Kraus V and Deberg M: Type II collagen markers in osteoarthritis: what do they indicate? Curr Opin Rheumatol. 19:444–450. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Bouchet BY, Colon M, Polotsky A, Shikani AH, Hungerford DS and Frondoza CG: Beta-1 integrin expression by human nasal chondrocytes in microcarrier spinner culture. J Biomed Mater Res. 52:716–724. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Rui Z, Li X, Fan J, Ren Y, Yuan Y, Hua Z, Zhang N and Yin G: GIT1Y321 phosphorylation is required for ERK1/2- and PDGF-dependent VEGF secretion from osteoblasts to promote angiogenesis and bone healing. Int J Mol Med. 30:819–825. 2012.PubMed/NCBI

29 

Pang J, Xu X, Wang X, Majumder S, Wang J, Korshunov VA and Berk BC: G-protein-coupled receptor kinase interacting protein-1 mediates intima formation by regulating vascular smooth muscle proliferation, apoptosis, and migration. Arterioscler Thromb Vasc Biol. 33:999–1005. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Pang J, Xu X, Getman MR, Shi X, Belmonte SL, Michaloski H, Mohan A, Blaxall BC and Berk BC: G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart. J Mol Cell Cardiol. 51:769–776. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Zhang S, Hisatsune C, Matsu-Ura T and Mikoshiba K: G-protein-coupled receptor kinase-interacting proteins inhibit apoptosis by inositol 1,4,5-triphosphate receptor-mediated Ca2+ signal regulation. J Biol Chem. 284:29158–29169. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang L, Zhao G, Xu X, Fang J, Chen J, Li J, Gao X, Hao L and Chen Y: Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression. Int J Mol Med 35: 1074-1080, 2015.
APA
Zhang, L., Zhao, G., Xu, X., Fang, J., Chen, J., Li, J. ... Chen, Y. (2015). Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression. International Journal of Molecular Medicine, 35, 1074-1080. https://doi.org/10.3892/ijmm.2015.2114
MLA
Zhang, L., Zhao, G., Xu, X., Fang, J., Chen, J., Li, J., Gao, X., Hao, L., Chen, Y."Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression". International Journal of Molecular Medicine 35.4 (2015): 1074-1080.
Chicago
Zhang, L., Zhao, G., Xu, X., Fang, J., Chen, J., Li, J., Gao, X., Hao, L., Chen, Y."Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression". International Journal of Molecular Medicine 35, no. 4 (2015): 1074-1080. https://doi.org/10.3892/ijmm.2015.2114
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang L, Zhao G, Xu X, Fang J, Chen J, Li J, Gao X, Hao L and Chen Y: Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression. Int J Mol Med 35: 1074-1080, 2015.
APA
Zhang, L., Zhao, G., Xu, X., Fang, J., Chen, J., Li, J. ... Chen, Y. (2015). Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression. International Journal of Molecular Medicine, 35, 1074-1080. https://doi.org/10.3892/ijmm.2015.2114
MLA
Zhang, L., Zhao, G., Xu, X., Fang, J., Chen, J., Li, J., Gao, X., Hao, L., Chen, Y."Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression". International Journal of Molecular Medicine 35.4 (2015): 1074-1080.
Chicago
Zhang, L., Zhao, G., Xu, X., Fang, J., Chen, J., Li, J., Gao, X., Hao, L., Chen, Y."Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression". International Journal of Molecular Medicine 35, no. 4 (2015): 1074-1080. https://doi.org/10.3892/ijmm.2015.2114
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