Skip to main content Skip to main navigation menu Skip to site footer

Plasma Vascular Endothelial Growth Factor (VEGF) profile and the association with synovial inflammation in knee osteoarthritis


Background Recent update of osteoarthritis (OA) pathophysiology is affected by inflammatory process of the synovium, which in turn plays the role in prevention of disease progression. It is believed that vascular endothelial growth factor (VEGF), an essential growth factor for vascular endothelial cells, is engaged in synovial inflammatory process that occurs in knee OA, but the association between circulating VEGF levels with synovial inflammation in knee OA is not well known.

Purpose: Identification of plasma VEGF profile and its association with synovial inflammation in knee OA patients.

Method: Consecutive cross-sectional study of primary knee OA patients with or without synovial inflammation. All research materials from history taking, physical examination, to imaging analysis such as ultrasound as well as measurement of plasma VEGF levels using ELISA were done and analysed using T-test, Spearman correlation test, Pearson correlation test, and multiple linear regression analysis (p= 0.05).

Result: There was significant increase of circulating plasma VEGF level in knee OA patients with synovial inflammation (p<0.05). Synovial inflammation was proven associated with high level of plasma VEGF level and influenced by overweight and degree of knee OA variable (p<0.05), but did not associate with existence of OA in other joints, accept OA therapy, hyperuricemia nor DM (p>0.05).

Conclusion Plasma VEGF levels are higher in knee OA with synovial inflammation, and there is an association between high plasma VEGF levels with the occurrence of synovial inflammation in knee OA.


  1. Roemer FW, Zhang Y, Niu J, Lynch JA, Crema MD, Marra MD, Nevitt MC, Felson DT, Hughes LB, El-Khoury GY, Englund M, Guermazi A. Tibiofemoral Joint Osteoarthritis: Risk Factors for MR-depicted Fast Cartilage Loss over a 30-month Period in the Multicenter Osteoarthritis Study. Radiology 2009; 252(3): 772–80. DOI: 10.1148/radiol.2523082197
  2. Baker K, Grainger A, Niu J, Clancy M, Guermazi A, Crema M, Hughes L, Buckwalter J, Wooley A, Nevitt M, Felson DT. Relation of Synovitis to Knee Pain using Contrast-enhanced MRI. Ann Rheum Dis 2009. DOI:10.1136/ard.2009.121426
  3. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, BresnihanB. Synovial Tissue Inflammation in Early and Late Osteoarthritis. Ann Rheum Dis 2005; 64:1263-7. DOI: 10.1136/ard.2004.025270
  4. D’Agostino MA, Conaghan PG, Bars ML, Baron G, Grassi W, Martin-Mola E, Wakefield R, Brasseur J-L, So A, Backhaus M, Malaise M, Burmester G, Schmidely N, Ravaud P, Dougados M, Emery P. EULAR Report on The Use of Ultrasonography in Painful Knee Osteoarthritis. Part 1: Prevalence of Inflammation in Osteoarthritis. Ann Rheum Dis 2005; 64:1703–9. DOI: 10.1136/ard.2005.037994
  5. Karim Z, Wakefield RJ, Quinn M, Conaghan PG, Brown AK, Veale DJ, O’Connor P, Reece R, Emery P. Validation and Reproducibility of Ultrasonography in The Detection of Synovitis in The Knee. Arthritis Rheum 2004; 50:387-94. DOI: 10.1002/art.20054
  6. Ferrara N, Houck K, Jakeman L. et al. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev. 1992; 13:18–32. DOI: 10.1210/edrv-13-1-18
  7. Yoo S, Kwok S, Kim W. Proinflammatory Role of Vascular Endothelial Growth Factor in the Pathogenesis of Rheumatoid Arthritis: Prospects for Therapeutic Intervention. Mediators of Inflammation 2008; 2008. DOI: :10.1155/2008/129873
  8. Altman, R. Development of Criteria for the Classification and Reporting of Osteoarthritis. Arthritis Rheum 1986; 29 (8):1039-1049. Pub Med PMID: 3741515
  9. Riyazi N, Meulenbelt I, Kroon HM, Ronday KH, Hellio le Graverand M-P,Rosendaal FR, Breedveld FC, Slagboom PE, Kloppenburg M. Evidence for Familial Aggregation of Hand, Hip, and Spine but not Knee Osteoarthritis in Siblings with Multiple Joint Involvement: the GARP Study. Ann Rheum Dis 2005; 64:438–43. DOI: 10.1136/ard.2004.024661
  10. Millet PJ, Gobezie R, Boykin RE. Shoulder Osteoarthritis : Diagnosis and Management. Am Fam Physician 2008; 78(5): 605-611. Pub Med PMID : 18788237
  11. Grunfeld R, Aydogan U, Juliano P, Bustillo J. Ankle arthritis: Diagnosis and Conservative Management. OA Musculoskeletal Medicine 2013;1(4):32. DOI: 1400362334
  12. Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, Wakefield RJ, O’Connor PJ, Emery P. Presence of Significant Synovitis in Rheumatoid Arthritis Patients With Disease-Modifying Antirheumatic Drug–Induced Clinical Remission Evidence From an Imaging Study May Explain Structural Progression. Arthritis & Rheumatis 2006; 54 (12) : 3761–3773. DOI: 10.1002/art.22190
  13. Sellam J, Berenbaum F. The Role of Synovitis in Pathophysiologyand Clinical Symptoms of Osteoarthritis. Nat. Rev. Rheumato 2010; 6: 625–35. DOI: 10.1038/nrrheum.2010.159
  14. Mabey T, Honsawek S, Saetan N, Poovorawan Y, Tanavele A, Yuktananda P. Angiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritis. International Orthopaedics 2014; 38 : 2885-1892. DOI : 10.1007/s00264-014-2406-y
  15. Saetan N, Honsawek S, Tanavalee A, Yuktanandana P, Meknavin S, Ngarmukos S, Tanpowpong T, Parkpian V. Relationship of plasma and synovial fluid vascular endothelial growth factor with radiographic severity in primary knee osteoarthritis. Int Orthop 2014; 38(5):1099-104. DOI : 10.1007/s00264-013-2192-y
  16. Bonnet CS, Walsh DA. Osteoarthritis, Angiogenesis and Inflammation. Rheumatology 2005; 44:7–16. DOI : 10.1093/rheumatology/keh344
  17. Haywood L, McWilliams DF, Pearson CI, Gill SE, Ganesan A, Wilson D, Walsh DA. Inflammation and Angiogenesis in Osteoarthritis. Arthritis & Rheumatism 2003; 48(8): 2173–7. DOI : DOI 10.1002/art.11094
  18. Attur M, Samuels J, Krasnokutsky S, Abramson SB. Targeting the Synovial Tissue for Treating Osteoarthritis (OA): Where is the Evidence?. Best Practice & Research Clinical Rheumatology 2010; 24: 71–9. DOI: 10.1016/j.berh.2009.08.011
  19. Levick JR, McDonald JN. Fluid Movement Across Synovium in Healthy Joints: Role of Synovial Fluid Macromolecules. Annals of the Rheumatic Diseases 1995; 54: 417-23. PMC1005608
  20. du Souich P. 2008. The Role of Synovitis in the Physiopathology of Osteoarthritis –Effects of Chondroitin Sulphate. European Muskuloskeletal Review. [Cited 2014 Sept 2]. Available from : URL :
  21. Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest 2007; 117: 2362–2368. DOI: 10.1172/JCI32239
  22. Murata M, Yudoh K, Masuko K. The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis. Osteoarthritis Cartilage 2008; 16:279-86. DOI: 10.1016/j.joca.2007.09.003
  23. van den Oever IAM, Raterman HG, Nurmohamed MT, Simsek S. Endothelial Dysfunction, Inflammation, and Apoptosis in Diabetes Mellitus. Mediators Inflamm. 2010: 792393. DOI : 10.1155/2010/792393
  24. Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal R, Mu W, Krotova K, Block ER, Prabhakar S, Johnson RJ. Hyperuricemia induces endothelial dysfunction. Kidney International 2005; 67: 1739–1742. DOI: 10.1111/j.1523-1755.2005.00273.x
  25. Kolluru GK, Bir SC, Kevil CG. Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing. International Journal of Vascular Medicine 2012; 2012. DOI : 10.1155/2012/918267

How to Cite

Martadiani, E. D., Kawiyana, I. K. S., Herawati, S., & Tjan, A. (2018). Plasma Vascular Endothelial Growth Factor (VEGF) profile and the association with synovial inflammation in knee osteoarthritis. Bali Medical Journal, 7(3).




Search Panel

Elysanti Dwi Martadiani
Google Scholar
BMJ Journal

I Ketut Siki Kawiyana
Google Scholar
BMJ Journal

Sianny Herawati
Google Scholar
BMJ Journal

Anastasia Tjan
Google Scholar
BMJ Journal