Soluble Mediators in Posttraumatic Wrist and Primary Knee Osteoarthritis

Document Type : RESEARCH PAPER


1 Department of Plastic Reconstructive and Hand Surgery University Medical Center, Utrecht, the Netherlands

2 Department of Orthopedic Surgery University Medical Center, Utrecht, the Netherlands

3 Department of Orthopedics & Department of Otorhinolaryngology Erasmus MC, University Medical Center, Rotterdam, The Netherlands


 New discoveries about the pathophysiology changed the concept that all forms of osteoarthritis are alike; this lead to the delineation of different phenotypes such as age, trauma or obese related forms. We aim to compare soluble mediator profiles in primary knee and posttraumatic wrist osteoarthritis. Based on the general faster progression rate of wrist osteoarthritis, we hypothesize a more inflammatory profile.
We collected synovial fluid from 20 primary osteoarthritic knee and 20 posttraumatic osteoarthritic wrist joints. 17 mediators were measured by multiplex enzyme-linked immunosorbent assay: chemokine ligand 5, interferon-γ, leukemia inhibitory factor, oncostatin-M, osteoprotegerin, tumor necrosis factor-α, vascular endothelial growth factor, interleukin (IL)-1α, IL-1β, IL-1 receptor antagonist, IL-4, IL-6, IL-7, IL-8, IL-10, IL-13 and IL-17.
 Ten mediators were higher in posttraumatic osteoarthritic synovial fluid: tumor necrosis factor-α (TNFα), IL-1α, IL-1RA, IL-6, IL-10, IL-17, oncostatin-M, interferon-γ, chemokine ligand 5 and leukemia inhibitory factor(P<0.001). IL-1ß, IL-4, IL-7 were not detected, TNFα was not detected in knee osteoarthritic synovial fluid. IL-8, IL-13, osteoprotegerin and vascular endothelial growth factor levels did not differ between the synovial fluid types.
 In general wrist osteoarthritis seems characterized by a stronger inflammatory response than primary knee osteoarthritis. More pronounced inflammatory mediators might offer a paradigm for the faster progression of posttraumatic osteoarthritis. Increase of specific mediators could form a possible target for future mediator modulating therapy in wrist osteoarthritis.


  1. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2010; 7:33-42.

  2. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115-26.

  3. Marsh JL, Weigel DP, Dirschl DR. Tibial plafond fractures. How do these ankles function over time? J Bone Joint Surg Am. 2003; 85-A:287-95.

  4. Knirk JL, Jupiter JB. Intra-articular fractures of the distal end of the radius in young adults. J Bone Joint Surg Am. 1986; 68:647-59.

  5. Lotz MK, Kraus VB. New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther. 2010; 12:211.

  6. Marsh JL, Buckwalter J, Gelberman R, Dirschl D, Olson S, Brown T, et al. Articular fractures: does an anatomic reduction really change the result? J Bone Joint Surg Am. 2002;84-A:1259-71.

  7. Rutgers M, Saris DB, Yang KG, Dhert WJ, Creemers LB. Joint injury and osteoarthritis: soluble mediators in the course and treatment of cartilage pathology. Immunotherapy. 2009; 1:435-45.

  8. Teunis T, Beekhuizen M, Kon M, Creemers LB, Schuurman AH, van Minnen LP. Inflammatory mediators in posttraumatic radiocarpal osteoarthritis. J Hand Surg Am. 2013; 38:1735-40.

  9. Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990; 33:1601-10.

  10. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004; 427:27-36.

  11. Fernandes JC, Martel-Pelletier J, Pelletier JP. The role of cytokines in osteoarthritis pathophysiology. Biorheology. 2002; 39:237-46.

  12. de Jager W, Prakken B, Rijkers GT. Cytokine multiplex immunoassay: methodology and (clinical) applications. Methods Mol Biol. 2009; 514:119-33.

  13. de Jager W, Prakken BJ, Bijlsma JW, Kuis W, Rijkers GT. Improved multiplex immunoassay performance in human plasma and synovial fluid following removal of interfering heterophilic antibodies. J Immunol Methods. 2005; 300:124-35.

  14. Knox P, Levick JR, McDonald JN. Synovial fluid--its mass, macromolecular content and pressure in major limb joints of the rabbit. Q J Exp Physiol. 1988;73:33-45.

  15. Kraan MC, Reece RJ, Smeets TJ, Veale DJ, Emery P, Tak PP. Comparison of synovial tissues from the knee joints and the small joints of rheumatoid arthritis patients: Implications for pathogenesis and evaluation of treatment. Arthritis Rheum. 2002; 46:2034-8.

  16. Rachakonda PS, Rai MF, Manning K, Schmidt MF. Expression of canine interleukin-4 in canine chondrocytes inhibits inflammatory cascade through STAT6. Cytokine. 2008; 44:179-84.

  17. Beekhuizen M, Gierman LM, van Spil WE, Van Osch GJ, Huizinga TW, Saris DB, et al. An explorative study comparing levels of soluble mediators in control and osteoarthritic synovial fluid. Osteoarthritis Cartilage. 2013; 21:918-22.

  18. Blom AB, van der Kraan PM, van den Berg WB. Cytokine targeting in osteoarthritis. Curr Drug Targets. 2007; 8:283-92.

  19. Marks PH, Donaldson ML. Inflammatory cytokine profiles associated with chondral damage in the anterior cruciate ligament-deficient knee. Arthroscopy. 2005;21:1342-7.

  20. Burger D, Dayer JM, Palmer G, Gabay C. Is IL-1 a good therapeutic target in the treatment of arthritis? Best Pract Res Clin Rheumatol. 2006;20:879-96.

  21. Schnitzer TJ. New pharmacologic approaches in the management of osteoarthritis. Arthritis Care Res (Hoboken). 2010;62:1174-80.

  22. Calich AL, Domiciano DS, Fuller R. Osteoarthritis: can anti-cytokine therapy play a role in treatment? Clin Rheumatol. 2010;29:451-5.