Skip to main content
Top
Published in: International Orthopaedics 1/2013

01-01-2013 | Original Paper

Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes

Authors: Paula Hoff, Frank Buttgereit, Gerd-Rüdiger Burmester, Manuela Jakstadt, Timo Gaber, Kristin Andreas, Georg Matziolis, Carsten Perka, Eric Röhner

Published in: International Orthopaedics | Issue 1/2013

Login to get access

Abstract

Purpose

Two of the most common joint diseases are rheumatoid arthritis (RA) and osteoarthritis (OA). Cartilage degradation and erosions are important pathogenetic mechanisms in both joint diseases and have presently gained increasing interest. The aim of the present study was to investigate the effects of the synovial fluid environment of OA patients in comparison with synovial fluids of RA patients on human chondrocytes in vitro.

Methods

Primary human chondrocytes were incubated in synovial fluids gained from patients with OA or RA. The detection of vital cell numbers was determined by histology and by using the Casy Cell Counter System. Cytokine and chemokine secretion was determined by a multiplex suspension array.

Results

Microscopic analysis showed altered cell morphology and cell shrinkage following incubation with synovial fluid of RA patients. Detection of vital cells showed a highly significant decrease of vital chondrocyte when treated with RA synovial fluids in comparison with OA synovial fluids. An active secretion of cytokines such as vascular endothelial growth factor (VEGF) of chondrocytes treated with OA synovial fluids was observed.

Conclusions

Significantly increased levels of various cytokines in synovial fluids of RA, and surprisingly of OA, patients were shown. Activation of pro-inflammatory cytokines of human chondrocytes by synovial fluids of OA patient supports a pro-inflammatory process in the pathogenesis of OA.
Literature
1.
go back to reference van der Kraan PM, van den Berg WB (2012) Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthr Cartil 20(3):223–232PubMedCrossRef van der Kraan PM, van den Berg WB (2012) Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthr Cartil 20(3):223–232PubMedCrossRef
2.
go back to reference Matsumoto S, Muller-Ladner U, Gay RE, Nishioka K, Gay S (1996) Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol 23(8):1345–1352PubMed Matsumoto S, Muller-Ladner U, Gay RE, Nishioka K, Gay S (1996) Ultrastructural demonstration of apoptosis, Fas and Bcl-2 expression of rheumatoid synovial fibroblasts. J Rheumatol 23(8):1345–1352PubMed
3.
go back to reference Szekanecz Z, Szucs G, Szanto S, Koch AE (2006) Chemokines in rheumatic diseases. Curr Drug Targets 7(1):91–102PubMedCrossRef Szekanecz Z, Szucs G, Szanto S, Koch AE (2006) Chemokines in rheumatic diseases. Curr Drug Targets 7(1):91–102PubMedCrossRef
4.
go back to reference Vergunst CE, Tak PP (2005) Chemokines: their role in rheumatoid arthritis. Curr Rheumatol Rep 7(5):382–388PubMedCrossRef Vergunst CE, Tak PP (2005) Chemokines: their role in rheumatoid arthritis. Curr Rheumatol Rep 7(5):382–388PubMedCrossRef
5.
go back to reference Braun J, Brandt J, Listing J, Zink A, Alten R, Burmester G, Golder W, Gromnica-Ihle E, Kellner H, Schneider M, Sorensen H, Zeidler H, Reddig J, Sieper J (2003) Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial. Arthritis Rheum 48(8):2224–2233PubMedCrossRef Braun J, Brandt J, Listing J, Zink A, Alten R, Burmester G, Golder W, Gromnica-Ihle E, Kellner H, Schneider M, Sorensen H, Zeidler H, Reddig J, Sieper J (2003) Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial. Arthritis Rheum 48(8):2224–2233PubMedCrossRef
6.
go back to reference Rau R (2010) Efficacy of methotrexate in comparison to biologics in rheumatoid arthritis. Clin Exp Rheumatol 28(5 Suppl 61):S58–S64PubMed Rau R (2010) Efficacy of methotrexate in comparison to biologics in rheumatoid arthritis. Clin Exp Rheumatol 28(5 Suppl 61):S58–S64PubMed
7.
go back to reference Rohner E, Matziolis G, Perka C, Fuchtmeier B, Gaber T, Burmester GR, Buttgereit F, Hoff P (2012) Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases. Immunol Res 52(3):169–175PubMedCrossRef Rohner E, Matziolis G, Perka C, Fuchtmeier B, Gaber T, Burmester GR, Buttgereit F, Hoff P (2012) Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases. Immunol Res 52(3):169–175PubMedCrossRef
8.
go back to reference Fernandes JC, Martel-Pelletier J, Pelletier JP (2002) The role of cytokines in osteoarthritis pathophysiology. Biorheology 39(1–2):237–246PubMed Fernandes JC, Martel-Pelletier J, Pelletier JP (2002) The role of cytokines in osteoarthritis pathophysiology. Biorheology 39(1–2):237–246PubMed
9.
go back to reference Stannus O, Jones G, Cicuttini F, Parameswaran V, Quinn S, Burgess J, Ding C (2010) Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr Cartil 18(11):1441–1447PubMedCrossRef Stannus O, Jones G, Cicuttini F, Parameswaran V, Quinn S, Burgess J, Ding C (2010) Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr Cartil 18(11):1441–1447PubMedCrossRef
10.
go back to reference Le TK, Montejano LB, Cao Z, Zhao Y, Ang D (2012) Healthcare costs associated with osteoarthritis in US patients. Pain Pract Le TK, Montejano LB, Cao Z, Zhao Y, Ang D (2012) Healthcare costs associated with osteoarthritis in US patients. Pain Pract
11.
go back to reference Rohner E, Kolar P, Seeger JB, Arnholdt J, Thiele K, Perka C, Matziolis G (2011) Toxicity of antiseptics against chondrocytes: what is best for the cartilage in septic joint surgery? Int Orthop 35(11):1719–1723PubMedCrossRef Rohner E, Kolar P, Seeger JB, Arnholdt J, Thiele K, Perka C, Matziolis G (2011) Toxicity of antiseptics against chondrocytes: what is best for the cartilage in septic joint surgery? Int Orthop 35(11):1719–1723PubMedCrossRef
12.
go back to reference Loeser RF (2009) Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthr Cartil 17(8):971–979PubMedCrossRef Loeser RF (2009) Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthr Cartil 17(8):971–979PubMedCrossRef
13.
go back to reference Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, Gale D, Grainger A, Conaghan P, Felson DT (2007) Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 66(12):1599–1603PubMedCrossRef Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, Gale D, Grainger A, Conaghan P, Felson DT (2007) Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 66(12):1599–1603PubMedCrossRef
14.
go back to reference Feldmann M, Maini SR (2008) Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev 223:7–19PubMedCrossRef Feldmann M, Maini SR (2008) Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev 223:7–19PubMedCrossRef
15.
go back to reference Uppal SS, Raghupathy R, Hayat SJ, Longenecker JC, Abraham M, Rawoot P (2010) Disease activity and cytokine production in mitogen-stimulated peripheral blood mononuclear cells from patients with rheumatoid arthritis. Med Princ Pract 19(1):33–39PubMedCrossRef Uppal SS, Raghupathy R, Hayat SJ, Longenecker JC, Abraham M, Rawoot P (2010) Disease activity and cytokine production in mitogen-stimulated peripheral blood mononuclear cells from patients with rheumatoid arthritis. Med Princ Pract 19(1):33–39PubMedCrossRef
16.
go back to reference Fearon U, Veale DJ (2007) Angiogenesis in arthritis: methodological and analytical details. Meth Mol Med 135:343–357CrossRef Fearon U, Veale DJ (2007) Angiogenesis in arthritis: methodological and analytical details. Meth Mol Med 135:343–357CrossRef
17.
go back to reference Koch AE (1998) Review: angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum 41(6):951–962PubMedCrossRef Koch AE (1998) Review: angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum 41(6):951–962PubMedCrossRef
18.
go back to reference Bauters C, Asahara T, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM (1995) Site-specific therapeutic angiogenesis after systemic administration of vascular endothelial growth factor. J Vasc Surg 21(2):314–324PubMedCrossRef Bauters C, Asahara T, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM (1995) Site-specific therapeutic angiogenesis after systemic administration of vascular endothelial growth factor. J Vasc Surg 21(2):314–324PubMedCrossRef
19.
go back to reference Lambert C, Mathy-Hartert M, Dubuc JE, Montell E, Verges J, Munaut C, Noel A, Henrotin Y (2012) Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate. Arthritis Res Ther 14(2):R58PubMedCrossRef Lambert C, Mathy-Hartert M, Dubuc JE, Montell E, Verges J, Munaut C, Noel A, Henrotin Y (2012) Characterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate. Arthritis Res Ther 14(2):R58PubMedCrossRef
20.
go back to reference Murata M, Yudoh K, Masuko K (2008) The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis? Osteoarthr Cartil 16(3):279–286PubMedCrossRef Murata M, Yudoh K, Masuko K (2008) The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis? Osteoarthr Cartil 16(3):279–286PubMedCrossRef
21.
go back to reference Lainer-Carr D, Brahn E (2007) Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis. Nat Clin Pract Rheumatol 3(8):434–442PubMedCrossRef Lainer-Carr D, Brahn E (2007) Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis. Nat Clin Pract Rheumatol 3(8):434–442PubMedCrossRef
22.
go back to reference Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H (2011) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7(1):33–42PubMedCrossRef Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H (2011) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7(1):33–42PubMedCrossRef
23.
go back to reference Merz D, Liu R, Johnson K, Terkeltaub R (2003) IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. J Immunol 171(8):4406–4415PubMed Merz D, Liu R, Johnson K, Terkeltaub R (2003) IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. J Immunol 171(8):4406–4415PubMed
24.
go back to reference Matsukawa A, Yoshimura T, Maeda T, Ohkawara S, Takagi K, Yoshinaga M (1995) Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J Immunol 154(10):5418–5425PubMed Matsukawa A, Yoshimura T, Maeda T, Ohkawara S, Takagi K, Yoshinaga M (1995) Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J Immunol 154(10):5418–5425PubMed
25.
go back to reference Melgarejo E, Medina MA, Sanchez-Jimenez F, Urdiales JL (2009) Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. Int J Biochem Cell Biol 41(5):998–1001PubMedCrossRef Melgarejo E, Medina MA, Sanchez-Jimenez F, Urdiales JL (2009) Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. Int J Biochem Cell Biol 41(5):998–1001PubMedCrossRef
Metadata
Title
Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes
Authors
Paula Hoff
Frank Buttgereit
Gerd-Rüdiger Burmester
Manuela Jakstadt
Timo Gaber
Kristin Andreas
Georg Matziolis
Carsten Perka
Eric Röhner
Publication date
01-01-2013
Publisher
Springer-Verlag
Published in
International Orthopaedics / Issue 1/2013
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-012-1724-1

Other articles of this Issue 1/2013

International Orthopaedics 1/2013 Go to the issue