International Orthopaedics

, Volume 33, Issue 4, pp 1171–1175 | Cite as

Relationship of plasma and synovial fluid BMP-7 with disease severity in knee osteoarthritis patients: a pilot study

  • Sittisak Honsawek
  • Maneerat Chayanupatkul
  • Aree Tanavalee
  • Manoon Sakdinakiattikoon
  • Benjamad Deepaisarnsakul
  • Pongsak Yuktanandana
  • Srihatach Ngarmukos
Original Paper

Abstract

The objective of this study was to investigate bone morphogenetic protein-7 (BMP-7) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine their relationship to disease severity. Thirty-two patients with knee OA and 15 healthy subjects were enrolled in the study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. BMP-7 levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The mean plasma BMP-7 concentration of the knee OA patients was significantly higher compared with that of healthy controls (12.1 ± 1.6 vs 3.5 ± 0.9 pg/ml, P = 0.001). Although BMP-7 levels in plasma were higher with respect to paired synovial fluid samples, the difference was not statistically significant (12.1 ± 1.6 vs 10.5 ± 2.2 pg/ml, P = 0.3). Subsequent analysis showed that plasma BMP-7 levels significantly correlated with disease severity (r = 0.77, P < 0.001). Furthermore, the synovial fluid levels of BMP-7 also correlated with disease severity (r = 0.60, P < 0.001). In addition, plasma BMP-7 levels showed a positive correlation with synovial fluid BMP-7 levels (r = 0.71, P < 0.001). Overexpression of BMP-7 in plasma and synovial fluid is related to progressive joint damage in knee OA. These findings suggest that BMP-7 might serve as a biochemical parameter for determining disease severity in primary knee OA and could play a potential role in cartilage protection and repair of OA.

Résumé

Le but de cette étude est de réaliser une investigation concernant les taux de BMP-7 au niveau plasmatique et synovial des patients présentant une arthrose primaire du genou (OA) et de déterminer leurs relations avec la sévérité de la pathologie. 32 patients présentant une OA du genou et 15 patients sains ont été enrôlés dans cette étude. Les radiographies face/profil du genou ont été réalisées de façon à déterminer le niveau d’altération cartilagineuse du genou atteint. L’importance de l’OA au niveau du genou a été classée selon les critères de Kellgren Lawrence et les taux de BMP7 au niveau du plasma et du liquide synovial ont été mesurés par absorption enzymatique. La concentration moyenne plasmatique de BMP7 des patients présentant une OA du genou était significativement plus élevée que chez les sujets sains (12.1+/−1.6vs 3.5 +/−0.9 pg/ml, P = 0.3001). Bien que les taux plasmatiques soient plus élevés, il n’en est pas de même au niveau du liquide synovial, la différence n’étant pas statistiquement significative (12.1 +/−1.6 vs 10.5 +/− 2.2 pg/ml, P = 0.3) En conséquence cette analyse montre que les taux plasmatiques de BMP7 sont corrélés de façon significative avec la sévérité de la pathologie (r = 0.77, P < 0.001). De façon comparative, les taux de BMP7 au niveau du liquide synovial sont aussi corrélés avec l’importance de la pathologie (r = 0.60,P < 0.001), de plus les taux plasmatiques de BMP7 sont corrélés positivement avec les taux de BMP7 synoviaux (r = 0.71, P < 0.001). L’augmentation de l’expression de la BMP7 plasmatique et synoviale est en relation avec les dommages articulaires du genou. Ceci nous permet de penser que le BMP7 est un paramètre biochimique qui permet de déterminer la sévérité de l’atteinte des genoux dans l’arthrose et peut jouer un rôle potentiel dans la protection du cartilage ou dans sa réparation.

References

  1. 1.
    Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling—genomic perspective. Int Orthop 31:799–805PubMedCrossRefGoogle Scholar
  2. 2.
    Chubinskaya S, Frank B, Michalska M, Kumar B, Merrihew CA, Thonar EJ, Lenz ME, Otten L, Rueger DC, Block JA (2006) Osteogenic protein 1 in synovial fluid from patients with rheumatoid arthritis or osteoarthritis: relationship with disease and levels of hyaluronan and antigenic keratan sulfate. Arthritis Res Ther 8:R73PubMedCrossRefGoogle Scholar
  3. 3.
    Chubinskaya S, Hurtig M, Rueger DC (2007) OP-1/BMP-7 in cartilage repair. Int Orthop 31:773–781PubMedCrossRefGoogle Scholar
  4. 4.
    Chubinskaya S, Kuettner KE (2003) Regulation of osteogenic proteins by chondrocytes. Int J Biochem Cell Biol 35:1323–1340PubMedCrossRefGoogle Scholar
  5. 5.
    Chubinskaya S, Merrihew C, Cs-Szabo G, Mollenhauer J, McCartney J, Rueger DC, Kuettner KE (2000) Human articular chondrocytes express osteogenic protein-1. J Histochem Cytochem 48:239–250PubMedGoogle Scholar
  6. 6.
    Doss F, Menard J, Hauschild M, Kreutzer HJ, Mittlmeier T, Müller-Steinhardt M, Müller B (2007) Elevated IL-6 levels in the synovial fluid of osteoarthritis patients stem from plasma cells. Scand J Rheumatol 36:136–139PubMedCrossRefGoogle Scholar
  7. 7.
    Fahlgren A, Chubinskaya S, Messner K, Aspenberg P (2006) A capsular incision leads to a fast osteoarthritic response, but also elevated levels of activated osteogenic protein-1 in rabbit knee joint cartilage. Scand J Med Sci Sports 16:456–462PubMedCrossRefGoogle Scholar
  8. 8.
    Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman BN, Aliabadi P (1995) The incidence and natural history of knee osteoarthritis in the elderly. Arthritis Rheum 38:1500–1505PubMedCrossRefGoogle Scholar
  9. 9.
    Flechtenmacher J, Huch K, Thonar EJ, Mollenhauer JA, Davies SR, Schmid TM, Puhl W, Sampath TK, Aydelotte MB, Kuettner KE (1996) Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes. Arthritis Rheum 39:1896–1904PubMedCrossRefGoogle Scholar
  10. 10.
    Hogan BL (1996) Bone morphogenetic proteins in development. Curr Opin Genet Dev 6:432–438PubMedCrossRefGoogle Scholar
  11. 11.
    Hogan BL (1996) Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 10:1580–1594PubMedCrossRefGoogle Scholar
  12. 12.
    Issack PS, DiCesare PE (2003) Recent advances toward the clinical application of bone morphogenetic proteins in bone and cartilage repair. Am J Orthop 32:429–436PubMedGoogle Scholar
  13. 13.
    Jelic M, Pecina M, Haspl M, Kos J, Taylor K, Maticic D, McCartney J, Yin S, Rueger D, Vukicevic S (2001) Regeneration of articular cartilage chondral defects by osteogenic protein-1 (bone morphogenetic protein-7) in sheep. Growth Factors 19:101–113PubMedCrossRefGoogle Scholar
  14. 14.
    Kaneko S, Satoh T, Chiba J, Ju C, Inoue K, Kagawa J (2000) Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther 6:71–79PubMedCrossRefGoogle Scholar
  15. 15.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502PubMedCrossRefGoogle Scholar
  16. 16.
    Loeser RF, Pacione CA, Chubinskaya S (2003) The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum 48:2188–2196PubMedCrossRefGoogle Scholar
  17. 17.
    Ozkaynak E, Rueger DC, Drier EA, Corbett C, Ridge RJ, Sampath TK, Oppermann H (1990) OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. Embo J 9:2085–2093PubMedGoogle Scholar
  18. 18.
    Park MC, Park YB, Lee SK (2008) Relationship of bone morphogenetic proteins to disease activity and radiographic damage in patients with ankylosing spondylitis. Scand J Rheumatol 37:200–204PubMedCrossRefGoogle Scholar
  19. 19.
    Pearle A, Scanzello C, George S, Mandl LA, DiCarlo EF, Peterson M, Sculco TP, Crow MK (2007) Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage 15:516–523PubMedCrossRefGoogle Scholar
  20. 20.
    Pecina M, Giltaij LR, Vukicevic S (2001) Orthopaedic applications of osteogenic protein-1 (BMP-7). Int Orthop 25:203–208PubMedCrossRefGoogle Scholar
  21. 21.
    Pecina M, Jelic M, Martinovic S, Haspl M, Vukicevic S (2002) Articular cartilage repair: the role of bone morphogenetic proteins. Int Orthop 26:131–136PubMedCrossRefGoogle Scholar
  22. 22.
    Pilichou A, Papassotiriou I, Michalakakou K, Fessatou S, Fandridis E, Papachristou G, Terpos E (2008) High levels of synovial fluid osteoprotegerin (OPG) and increased serum ratio of receptor activator of nuclear factor-kappaB ligand (RANKL) to OPG correlate with disease severity in patients with primary knee osteoarthritis. Clin Biochem 41:746–749PubMedCrossRefGoogle Scholar
  23. 23.
    Rueger DC, Chubinskaya S (2004) BMPs in articular cartilage repair. In: Vukicevic S, Sampath KT (eds) Bone morphogenetic proteins: regeneration of bone and beyond. Birkhauser, Basel, pp 109–132Google Scholar
  24. 24.
    Söder S, Hakimiyan A, Rueger DC, Kuettner KE, Aigner T, Chubinskaya S (2005) Antisense inhibition of osteogenic protein-1 disturbs human articular cartilage integrity. Arthritis Rheum 52:468–478PubMedCrossRefGoogle Scholar
  25. 25.
    Urist MR (1965) Bone: formation by autoinduction. Science 150:893–899PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sittisak Honsawek
    • 1
    • 3
    • 5
  • Maneerat Chayanupatkul
    • 2
  • Aree Tanavalee
    • 3
  • Manoon Sakdinakiattikoon
    • 4
  • Benjamad Deepaisarnsakul
    • 1
  • Pongsak Yuktanandana
    • 3
  • Srihatach Ngarmukos
    • 3
  1. 1.Department of Biochemistry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Department of Physiology, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  3. 3.Department of Orthopaedics, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  4. 4.Department of Orthopaedic SurgeryBangkok Metropolitan Administration General HospitalBangkokThailand
  5. 5.Departments of Biochemistry and Orthopaedics, Faculty of MedicineChulalongkorn UniversityBangkokThailand

Personalised recommendations