Changes in Synovial Fluid Inflammatory Mediators and Cartilage Biomarkers After Experimental Acute Equine Synovitis

Open access


The purpose of the study was to define transient changes in the concentration of inflammatory biomarkers and cartilage biomarkers in the synovial fluid of joints following experimentally induced acute equine synovitis. Acute synovitis was induced in eight skeletally mature mares by a sterile intra-articular injection of 1 mL of phosphate-buffered saline (PBS) containing 0.5 ng of lipopolysaccharide (LPS). The solution was injected into the right middle carpal joint. One mL of sterile PBS was injected into the left control joint. Synovial fluid was obtained at the baseline level and at 8, 24, and 168 h after injection. The levels of inflammatory biomarkers-prostaglandin E2 (PGE2), interleukin 1β (IL-1β), and tumour necrosis factor-α (TNF-α), and cartilage turnover biomarkers-collagenase-cleavage neoepitope of type II collagen (C2C) and C-terminal crosslinked telopeptide type II collagen (CTX-II) were detected with proper assays. Single injections of LPS raised the number of synovial white blood cells and concentrations of total protein, PGE2, IL-1β, TNF-α, C2C, and CTX-II. PGE2 and IL-1β rose sharply at 8 h, while TNF-α increased steadily through 8 h and 24 h, at that point; these three factors returned to the baseline level by 168 h. The time course of C2C and CTX-II concentrations peaked sharply at 24 h, and continued to be significantly elevated over the baseline level even at 168 h. Injections of LPS into the joints led to a temporal inflammatory response, which in turn increased local release of inflammatory biomarkers and significantly altered the concentrations of cartilage markers in the synovial fluid.

1. Caron J.P, Gandy J.C, Schmidt M., Hauptman J.G., Sordillo L.M.: Influence of corticosteroids on interleukin-1β stimulated equine chondrocyte gene expression. Vet Surg 2013, 42, 231-237.

2. Christgau S, Garnero P., Fledelius C, Moniz C, Ensig M, Gineyts E., Rosenquist C, Qvist P.: Collagen type II C-telopeptide fragments as an index of cartilage degradation. Bone 2001, 29, 209-215.

3. de Grauw J.C., Brama P.A, Wiemer P., Brommer H., van de Lest C.H., van Weeren P.R.: Cartilage-derived biomarkers and lipid mediators of inflammation in horses with osteochondritis dissecans of the distal intermediate ridge of the tibia. Am J Vet Res 2006, 67, 1156-1162.

4. de Grauw J.C., van de Lest C.H, van Weeren P.R.: Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther 2009, 11, R35.

5. Hill CL, Hunter D.J, Niu J, Clancy M, Guermazi A, Genant H, Gale D, Grainger A, Conaghan P, Felson D.T.: Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 2007, 66, 1599-1603.

6. Jouglin M, Robert C, Valette J.P, Gavard F, Quintin-Colonna F, Denoix J.M.: Metalloproteinases and tumor necrosis factor-alpha activities in synovial fluids of horses: correlation with articular cartilage alterations. Vet Res 2000, 31, 507-515.

7. Kaspiris A, Khaldi L, Grivas T.B, Vasiliadis E, Kouvaras I, Dagkas S, Chronopoulos E, Papadimitriou E.: Subchondral cyst development and MMP-1 expression during progression of osteoarthritis: an immunohistochemical study. Orthop Traumatol Surg Res 2013, 99, 523-529.

8. Kunisch E, Kinne R.W., Alsalameh R.J, Alsalameh S.: Pro-inflammatory IL-1beta and/or TNF-alpha up-regulate matrix metalloproteases-1 and -3 mRNA in chondrocyte subpopulations potentially pathogenic in osteoarthritis: in situ hybridization studies on a single cell level. Int J Rheum Dis 2014. Epub ahead of print.

9. Lim H, Kim H.P.: Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. Arch Pharm Res 2011, 34, 109-117.

10. Lindegaard C, Gleerup K.B, Thomsen M.H, Martinussen T, Jacobsen S, Andersen P.H.: Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis. Am J Vet Res 2010, 71, 69-75.

11. Lohmander L.S, Atley L.M, Pietka T.A, Eyre D.R.: The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis. Arthritis Rheum 2003, 48, 3130-3139.

12. Maldonado M, Nam J.: The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis. Biomed Res Int 2013, doi: 10.1155/2013/284873.

13. Matyas J.R, Atley L, Ionescu M, Eyre D.R, Poole A.R.: Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis. Arthritis Rheum 2004, 50, 543-552.

14. Mobasheri A.: Osteoarthritis year 2012 in review: biomarkers. Osteoarthritis Cartilage 2012, 20, 1451-1464.

15. Morton AJ, Campbell N.B, Gayle J.M, Redding W.R, Blikslager A.T.: Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci 2005, 78, 189-192.

16. Oestergaard S., Chouinard L., Doyle N., Smith S.Y., Tankó L.B., Qvist P: Early elevation in circulating levels of C-telopeptides of type II collagen predicts structural damage in articular cartilage in the rodent model of collagen–induced arthritis. Arthritis Rheum 2006, 54, 2886–2890.

17. Petrov R., MacDonald M.H., Tesch A.M., Benton H.P.: Inhibition of adenosine kinase attenuates interleukin-1- and lipopolysaccharide-induced alterations in articular cartilage metabolism. Osteoarthr Cartilage 2005, 13, 250–257.

18. Ross M.W.: The lameness score: quantification of lameness severity. In: Diagnosis and Management of Lameness in the Horse. Edited by Ross M.W., Dyson S.J., Philadelphia: W.B. Saunders, 2003, pp. 66–67.

19. Ross T.N., Kisiday J.D., Hess T., McIlwraith C.W.: Evaluation of the inflammatory response in experimentally induced synovitis in the horse: a comparison of recombinant equine interleukin 1 beta and lipopolysaccharide. Osteoarthritis Cartilage 2012, 20, 1583–1590.

20. Scanzello C.R., Goldring S.R.: The role of synovitis in osteoarthritis pathogenesis. Bone 2012, 51, 249–257.

21. Sellam J., Berenbaum F.: The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 2010, 6, 625–635.

22. Tchetina E.V, Di Battista J.A., Zukor D.J, Antoniou J, Poole A.R.: Prostaglandin PGE2 at very low concentrations suppresses collagen cleavage in cultured human osteoarthritic articular cartilage: this involves a decrease in expression of proinflammatory genes, collagenases and COL10A1, a gene linked to chondrocyte hypertrophy. Arthritis Res Ther. 2007, 9, R75.

23. Todhunter P.G, Kincaid S.A., Todhunter R.J, Kammermann J.R, Johnstone B., Baird A.N, Hanson R.R, Wright J.M., Lin H.C, Purohit R.C.: Immunohistochemical analysis of an equine model of synovitis-induced arthritis. Am J Vet Res 1996, 57, 1080-1093.

24. Trumble T.N, Brown M.P, Merritt K.A., Billinghurst R.C.: CTX II (Cartilaps) assay using equine synovial fluid. Osteoarthr Cartilage 2006, 14, 70-71.

25. van den Boom R, van de Lest C.H, Bull S, Brama R.A., van Weeren P.R, Barneveld A: Influence of repeated arthrocentesis and exercise on synovial fluid concentrations of nitric oxide, prostaglandin E2 and glycosaminoglycans in healthy equine joints. Equine Vet J 2005, 37, 250-256.

26. van Loon J.P., de Grauw J.C, van Dierendonck M, Lami J.J, Back W, van Weeren P.R.: Intra-articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model. Equine Vet J 2010, 42, 412-419.

Bulletin of the Veterinary Institute in Pulawy

The Journal of National Veterinary Research Institute in Pulawy

Journal Information

IMPACT FACTOR 2017: 0.811
5-year IMPACT FACTOR: 0.973

CiteScore 2017: 0.68

SCImago Journal Rank (SJR) 2017: 0.287
Source Normalized Impact per Paper (SNIP) 2017: 0.484


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 163 163 24
PDF Downloads 51 51 11