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The effect of vascular endothelial growth factor on aggrecan and type II collagen expression in rat articular chondrocytes

Rheumatology International volume 32, pages 3359–3364 (2012)Cite this article

Abstract

The expression of vascular endothelial growth factor (VEGF) directly correlates with the Mankin score and the degree of cartilage destruction. The biological activity of VEGF on articular cartilage remains unknown, so this study was performed to investigate the effect of VEGF on aggrecan and type II collagen expression in vitro. We carried out this study at the Center Laboratory of Renmin Hospital at Wuhan University. Rat articular chondrocytes were cultured in a monolayer. Then, the experiment was divided into 4 groups: group A (control group), without any disposal; group B, treated with 10 ng/ml VEGF; group C, treated with 10 ng/ml IL-1β; and group D, treated with 10 ng/ml VEGF + 10 ng/ml IL-1β. After 48 h, messenger RNA (mRNA) expression of aggrecan and type II collagen was evaluated by real-time polymerase chain reaction (real-Time PCR), and protein expression of aggrecan and type II collagen was detected by Western blotting. VEGF was found to significantly inhibit the expression of aggrecan and type II collagen at the gene and protein levels. These findings suggest that VEGF may result in degeneration of articular cartilage by inhibiting the synthesis and expression of aggrecan and type II collagen.

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References

  1. Sharma L, Kapoor D, Issa S (2006) Epidemiology of osteoarthritis: an update. Curr Opin Rheumatol 18(2):147–156

    PubMed  Article  Google Scholar 

  2. Pfander D, Körtje D, Zimmermann R, Weseloh G, Kirsch T, Gesslein M, Cramer T, Swoboda B (2001) Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints. Ann Rheum Dis 60(11):1070–1073

    PubMed  Article  CAS  Google Scholar 

  3. Enomoto H, Inoki I, Komiya K, Shiomi T, Ikeda E, Obata K, Matsumoto H, Toyama Y, Okada Y (2003) Vascular endothelial growth factor isoforms and their receptors are expressed in human osteoarthritic cartilage. Am J Pathol 162(1):171–181

    PubMed  Article  CAS  Google Scholar 

  4. Inoue K, Masuko-Hongo K, Okamoto M, Nishioka K (2005) Induction of vascular endothelial growth factor and matrix metalloproteinase-3 (stromelysin) by interleukin-1 in human articular chondrocytes and synoviocytes. Rheumatol Int 26(2):93–98

    PubMed  Article  CAS  Google Scholar 

  5. Kim WU, Kang SS, Yoo SA, Hong KH, Bae DG, Lee MS, Hong SW, Chae CB, Cho CS (2006) Interaction of vascular endothelial growth factor 165 with neuropilin-1 protects rheumatoid synoviocytes from apoptotic death by regulating Bcl-2 expression and Bax translocation. J Immunol 177(8):5727–5735

    PubMed  CAS  Google Scholar 

  6. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossifi cation and angiogenesis during endochondral bone formation. Nat Med 5(6):623–628

    PubMed  Article  CAS  Google Scholar 

  7. Hulejová H, Baresová V, Klézl Z, Polanská M, Adam M, Senolt L (2007) Increased level of cytokines and matrix metalloproteinases in osteoarthritic subchondral bone. Cytokine 38(3):151–156

    PubMed  Article  Google Scholar 

  8. Cook JL, Anderson CC, Kreeger JM, Tomlinson JL (2000) Effects of human recombinant interleukin-1beta on canine articular chondrocytes in three-dimensional culture. Am J Vet Res 61(7):766–770

    PubMed  Article  CAS  Google Scholar 

  9. Goldring MB (2001) Anticytokine therapy for osteoarthritis. Expert Opin Biol Ther 1(5):817–829

    PubMed  Article  CAS  Google Scholar 

  10. Espanha MM (2010) Articular cartilage: structure and histochemical composition. Acta Reumatol Port 35(5):424–433

    PubMed  Google Scholar 

  11. Meredith JE Jr, Fazeli B, Schwartz MA (1993) The extracellular matrix as a cell survival factor. Mol Biol Cell 4(9):953–961

    PubMed  CAS  Google Scholar 

  12. Yang C, Li SW, Helminen HJ, Khillan JS, Bao Y, Prockop DJ (1997) Apoptosis of chondrocytes in transgenic mice lacking collagen II. Exp Cell Res 235(2):370–373

    PubMed  Article  CAS  Google Scholar 

  13. Cao L, Yang BB (1999) Chondrocyte apoptosis induced by aggrecan G1 domain as a result of decreased cell adhesion. Exp Cell Res 246(2):527–537

    PubMed  Article  CAS  Google Scholar 

  14. Rosenthal AK, Gohr CM, Ninomiya J, Wakim BT (2011) Proteomic analysis of articular cartilage vesicles from normal and osteoarthritic cartilage. Arthr Rheum 63(2):401–411

    Article  CAS  Google Scholar 

  15. Wu JJ, Woods PE, Eyre DR (1992) Identification of cross-linking sites in bovine cartilage type IX collagen reveals an antiparallel type II-type IX molecular relationship and type IX to type IX bonding. J Biol Chem 267(32):23007–23014

    PubMed  CAS  Google Scholar 

  16. Paulsen F, Tillmann B (1999) Composition of the extracellular matrix in human cricoarytenoid joint articular cartilage. Arch Histol Cytol 62(2):149–163

    PubMed  Article  CAS  Google Scholar 

  17. Murphy CL (2010) HIF-2alpha–a mediator of osteoarthritis? Cell Res 20(9):977–979

    PubMed  Article  Google Scholar 

  18. Mentlein R, Held-Feindt J (2003) Angiogenesis factors in gliomas-a new key to tumour therapy? Naturwissenschaften 90(9):385–394

    PubMed  Article  CAS  Google Scholar 

  19. Keramidas M, Faudot C, Cibiel A, Feige JJ, Thomas M (2008) Mitogenic functions of endocrine gland-derived vascular endothelial growth factor and Bombina variegata 8 on steroidogenic adrenocortical cells. J Endocrinol 196(3):473–482

    PubMed  Article  CAS  Google Scholar 

  20. Alvarez J, Costales L, López-Muñiz A, López JM (2005) Chondrocytes are released as viable cells during cartilage resorption associated with the formation of intrachondral canals in the rat tibial epiphysis. Cell Tissue Res 320(3):501–507

    PubMed  Article  Google Scholar 

  21. Nagai H, Aoki M (2002) Inhibition of growth plate angiogenesis and endochondral ossification with diminished expression of MMP-13 in hypertrophic chondrocytes in FGF-2-treated rats. J Bone Miner Metab 20(3):142–147

    PubMed  Article  CAS  Google Scholar 

  22. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5(6):623–628

    PubMed  Article  CAS  Google Scholar 

  23. Jingushi S, Scully SP, Joyce ME, Sugioka Y, Bolander ME (1995) Transforming growth factor-beta 1 and fibroblast growth factors in rat growth plate. J Orthop Res 13(5):761–768

    PubMed  Article  CAS  Google Scholar 

  24. Pufe T, Lemke A, Kurz B, Petersen W, Tillmann B, Grodzinsky AJ (2004) Mechanical overload induces VEGF in cartilage discs via hypoxia-inducible factor (HIF). Am J Pathol 164(1):185–192

    PubMed  Article  CAS  Google Scholar 

  25. Zhou JL, Liu SQ, Qiu B, Hu QJ, Ming JH, Peng H (2009) Effects of hyaluronan on vascular endothelial growth factor and receptor-2 expression in a rabbit osteoarthritis model. J Orthop Sci 14(3):313–319

    PubMed  Article  CAS  Google Scholar 

  26. Goldring MB (2000) Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2(6):459–465

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by fund from the Health Department (NO. JX4B15) and Wuhan University (NO. 3081016) of Hubei Province of China.

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We certify that there is no actual or potential conflict of interest in relation to this article.

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Affiliations

  1. Department of Orthopedics, Renmin Hospital of Wuhan University, Jie Fang Road 238, Wuhan, 430060, Hubei Province, People’s Republic of China

    Xuan-yin Chen, Zhe Wang, Jian-lin Zhou, Qi-xue Jia & Bo Qiu

  2. Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People’s Republic of China

    Ya-rong Hao

Authors
  1. Xuan-yin Chen
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  2. Ya-rong Hao
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  3. Zhe Wang
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  4. Jian-lin Zhou
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  5. Qi-xue Jia
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  6. Bo Qiu
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Corresponding author

Correspondence to Bo Qiu.

Additional information

Xuan-yin Chen and Ya-rong Hao contributed equally to this work as co-first authors.

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Chen, Xy., Hao, Yr., Wang, Z. et al. The effect of vascular endothelial growth factor on aggrecan and type II collagen expression in rat articular chondrocytes. Rheumatol Int 32, 3359–3364 (2012). https://doi.org/10.1007/s00296-011-2178-2

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  • DOI: https://doi.org/10.1007/s00296-011-2178-2

Keywords

  • Vascular endothelial growth factor
  • Osteoarthritis
  • Cartilage
  • Aggrecan
  • Type II collagen