Subscribe to RSS
DOI: 10.3415/VCOT-16-11-0157
Correlation of dickkopf-1 concentrations in plasma and synovial fluid to the severity of radiographic signs of equine osteoarthritis
This study was supported in part by the Hunter Jumper Association of Michigan.
Publication History
Received:
22 November 2016
Accepted:
19 April 2017
Publication Date:
23 December 2017 (online)

Summary
Objective: The purpose of this study was to determine whether there was a correlation between circulating and intra-synovial Dkk-1 and radiographic signs of equine osteoarthritis.
Methods: Circulating and intra-synovial Dkk-1 levels were measured in clinical cases using a commercially available human Dkk-1 ELISA. Radiographs were performed of the joints from which fluid was collected and these were assessed and scored by a boarded radiologist for joint narrowing, subchondral bone sclerosis, subchondral bone lysis, and periarticular modelling. Comparisons were made between radiographic scores and the concentrations of Dkk-1 using a Kruskal-Wallis one-way ANOVA. Correlations were calculated using Kendall’s statistic.
Results: A total of 42 synovial fluid samples from 21 horses were collected and used in the analysis. No significant correlation was identified between Dkk-1 concentrations and radiographic signs of osteoarthritis. Intrasynovial Dkk-1 concentrations were significantly greater (p <0.001) in low motion joints (mean concentration, 232.68 pg/mL; range, 109.07–317.17) when compared to high- motion joints (28.78 pg/mL; 0.05–186.44 pg/mL) (p <0.001).
Clinical significance: Low motion joints have significantly higher concentrations of Dkk-1 compared to high motion joints. Further research is needed to establish the importance of this finding and whether potential diagnostic or therapeutic applications of Dkk-1 exist in the horse.
Supplementary material for this article is available at https://doi.org/10.3415/VCOT-16-11-0157
-
References
- 1 Kidd JA, Fuller C, Barr ARS. Osteoarthritis in the horse. Eq Vet Educ 2001; 13: 160-168.
- 2 Schlueter AE, Orth MW. Equine osteoarthritis: a brief review of the disease and its causes. Equine and Comparative Exercise Physiology. Cambridge University Press; 2004; 1: 221-31.
- 3 Bertone AL, Ishihara A, Zekas LJ. et al. Evaluation of a single intra-articular injection of autologous protein solution for treatment of osteoarthritis in horses. Am J Vet Res 2014; 75: 141-151.
- 4 Mirza MM, Bommala P, Richbourg HA. Gait changes vary among horses with naturally occurring osteoarthritits following intra-articular administration of autologous platelet-rich plasma. Front Vet Sci 2016; 3: 29.
- 5 Soto SA, Barbara AC. Bisphosphonates: pharmacology and clinical approach to their use in equine osteoarticular diseases. J Equine Vet Sci 2014; 34: 727-737.
- 6 Diarra D, Stolina M, Polzer K. et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13: 156-163.
- 7 Funck-Brentano T, Bouaziz W, Marty C. et al. Dkk-1-mediated inhibition of Wnt signaling in bone ameliorates osteoarthritis in mice. Arthritis Rheum 2014; 66: 3028-3039.
- 8 Lane NE, Nevitt MC, Lui L-Y. et al. Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women. Arthritis Rheum 2007; 56: 3319-3325.
- 9 Morvan F, Boulukos K, Clement-Lacroix P. et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Min Res 2006; 21: 934-945.
- 10 Li J, Sarosi I, Cattley RC. et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 2006; 39: 754-766.
- 11 Honsawek S, Tanavalee A, Yuktanandana P. et al. Dickkopf-1 (DKK-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients. BMC Musculoskelet Disord 2010; 11: 257.
- 12 Duesterdieck-Zellmer K, Semevolos S, Kinsley M. et al. Age-related differential gene and protein expression in postnatal cartilage canal and osteochondral junction chondrocytes. Gene Expr Patterns 2015; 17: 1-10.
- 13 Kinsley MA, Semevolos SA, Duesterdieck-Zellmer KF. Wnt/B-catenin signaling of cartilage canal and osteochondral junction chondrocytes and full thickness cartilage in early equine osteochondrosis. J Orthop Res 2015; 33: 1433-1438.
- 14 Weng L-H, Wang C-J, Ko J-Y. et al. Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral deterioration in osteoarthritis knees. Arthritis Rheum 2010; 62: 1393-1402.
- 15 Byam-Cook KL, Singer ER. Is there a relationship between clinical presentation, diagnostic and radiographic findings and outcome in horses with osteoarthritis of the small tarsal joints. Equine Vet J 2009; 41: 118-123.
- 16 Rossini M, Viapiana O, Idolazzi L. et al. Higher level of dickkopf-1 is associated with low bone mineral density and higher prevalence of vertebral fractures in patients with ankylosing spondylitis. Calcif Tissue Int 2015; 98: 438-445.
- 17 Goodrich LR, Nixon AJ. Medical treatment of osteoarthritis in the horse - a review. The Vet J 2006; 171: 51-69.
- 18 Mason JB, Gurda BL, Hankenson KD. et al. Wnt10b and Dkk-1 gene therapy differentially influenced trabecular bone architecture, soft tissue integrity, and osteophytosis in skeletally mature rat model of osteoarthritis. Connective Tissue Res 2016 December 9 [Epub ahead of print].