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)
![](https://www.thieme-connect.de/media/10.1055-s-00035023/201705/lookinside/thumbnails/10-3415-vcot-16-11-0157-1.jpg)
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].