J Vet Sci.  2008 Sep;9(3):317-325. 10.4142/jvs.2008.9.3.317.

Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for osteoarthritis in canine hip dysplasia

Affiliations
  • 1Department of Veterinary Preclinical Science, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand. korakot@chiangmai.ac.th
  • 2Thailand Excellence Center for Tissue Engineering, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Abstract

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 +/- 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 +/- 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 +/- 100.05 ng/ml) was significantly lower than that in the non-HD group (136 +/- 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 +/- 59.71 ng/ml) was lower than that in the non HD group (245.45 +/- 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs.

Keyword

biomarker; chondroitin sulfate; dog; hip dysplasia; osteoarthritis

MeSH Terms

Animals
Biological Markers/*blood
Body Weight
Chondroitin Sulfates/*blood
Dog Diseases/*blood
Dogs
Enzyme-Linked Immunosorbent Assay
Female
Hip Dysplasia, Canine/*blood/epidemiology
Hyaluronic Acid/*blood
Male
Osteoarthritis/blood/*veterinary
Prevalence
Sex Characteristics

Figure

  • Fig. 1 The levels of serum chondroitin sulfate epitope 3B3 (A) and WF6 (B) and hyaluronan (C) in the non-hip dysplasia (HD) group compared to the HD group. Data show the mean ± SD. *The significant difference (p < 0.05) between the non-HD and HD groups.

  • Fig. 2 The levels of serum chondroitin sulfate epitope 3B3 (A) and WF6 (B) and hyaluronan (C) in the non-hip dysplasia group. This group was categorized into 5 different subgroup due to body weight such as group 1 (less than 10 kg, n = 15), group 2 (from 10 kg to less than 15 kg, n = 30), group 3 (from 15 kg to less than 20 kg, n = 28), group 4 (from 20 kg to less than 25 kg, n = 15) and group 5 (greater than or equal to 25 kg, n = 10). No significant difference (p > 0.05) was observed among the subgroups.

  • Fig. 3 The levels of serum chondroitin sulfate epitope 3B3 (A), WF6 (B) and hyaluronan (C) in the non-HD group. The animals of this group were categorized into the male and female group. Data show the mean ± SD. No significant difference (p > 0.05) was observed between the genders.


Cited by  1 articles

The effect of doxycycline on canine hip osteoarthritis: design of a 6-months clinical trial
Korakot Nganvongpanit, Peraphan Pothacharoen, Niyada Suwankong, Siriwan Ong-Chai, Prachya Kongtawelert
J Vet Sci. 2009;10(3):239-247.    doi: 10.4142/jvs.2009.10.3.239.


Reference

1. Allan G. Thrall DE, editor. Radiographic signs of joint disease. Textbook of Veterinary Diagnostic Radiology. 1994. 2nd ed. Philadelphia: Saunders;130–150.
2. Alwan WH, Carter SD, Bennett D, Edwards GB. Glycosaminoglycans in horses with osteoarthritis. Equine Vet J. 1991. 23:44–47.
3. Antonas KN, Fraser JR, Muirden KD. Distribution of biologically labelled radioactive hyaluronic acid injected into joints. Ann Rheum Dis. 1973. 32:103–111.
Article
4. Arican M, Carter SD, May C, Bennett D. Hyaluronan in canine arthropathies. J Comp Pathol. 1994. 111:185–195.
Article
5. Belcher C, Yaqub R, Fawthrop F, Bayliss M, Doherty M. Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees. Ann Rheum Dis. 1997. 56:299–307.
Article
6. Björk J, Kleinau S, Tengblad A, Smedegård G. Elevated levels of serum hyaluronate and correlation with disease activity in experimental models of arthritis. Arthritis Rheum. 1989. 32:306–311.
Article
7. Blom AB, van der Kraan PM, van den Berg WB. Cytokine targeting in osteoarthritis. Curr Drug Targets. 2007. 8:283–292.
Article
8. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther. 2006. 8:R187.
9. Bruyere O, Collette JH, Ethgen O, Rovati LC, Giacovelli G, Henrotin YE, Seidel L, Reginster JY. Biochemical markers of bone and cartilage remodeling in prediction of longterm progression of knee osteoarthritis. J Rheumatol. 2003. 30:1043–1050.
10. Budsberg SC, Lenz ME, Thonar EJ. Serum and synovial fluid concentrations of keratan sulfate and hyaluronan in dogs with induced stifle joint osteoarthritis following cranial cruciate ligament transection. Am J Vet Res. 2006. 67:429–432.
Article
11. Cardinet GH 3rd, Kass PH, Wallace LJ, Guffy MM. Association between pelvic muscle mass and canine hip dysplasia. J Am Vet Med Assoc. 1997. 210:1466–1473.
12. Caterson B, Flannery CR, Hughes CE, Little CB. Mechanisms involved in cartilage proteoglycan catabolism. Matrix Biol. 2000. 19:333–344.
Article
13. Caterson B, Griffin J, Mahmoodian F, Sorrell JM. Monoclonal antibodies against chondroitin sulphate isomers: their use as probes for investigating proteoglycan metabolism. Biochem Soc Trans. 1990. 18:820–823.
Article
14. Caterson B, Hughes CE, Roughley P, Mort JS. Anabolic and catabolic markers of proteoglycan metabolism in osteoarthritis. Acta Orthop Scand Suppl. 1995. 266:121–124.
Article
15. Caterson B, Mahmoodian F, Sorrell JM, Hardingham TE, Bayliss MT, Carney SL, Ratcliffe A, Muir H. Modulation of native chondroitin sulphate structure in tissue development and in disease. J Cell Sci. 1990. 97:411–417.
Article
16. DeAngelis PL. Hyaluronan synthases: fascinating glycosyltransferases from vertebrates, bacterial pathogens, and algal viruses. Cell Mol Life Sci. 1999. 56:670–682.
Article
17. Fuller CJ, Barr AR, Sharif M, Dieppe PA. Cross-sectional comparison of synovial fluid biochemical markers in equine osteoarthritis and the correlation of these markers with articular cartilage damage. Osteoarthritis Cartilage. 2001. 9:49–55.
Article
18. George J, Stern R. Serum hyaluronan and hyaluronidase: very early markers of toxic liver injury. Clin Chim Acta. 2004. 348:189–197.
Article
19. Goldberg RL, Rubin AS. Serum hyaluronate as a marker for disease severity in the Lactobacillus casei model of arthritis in the rat. J Rheumatol. 1989. 16:92–96.
20. Hazell PK, Dent C, Fairclough JA, Bayliss MT, Hardingham T. Changes in glycosaminoglycan epitope levels in knee joint fluid following injury. Arthritis Rheum. 1995. 38:953–959.
Article
21. Hegemann N, Kohn B, Brunnberg L, Schmidt MF. Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders. Osteoarthritis Cartilage. 2002. 10:714–721.
Article
22. Heinegård D, Hascall VC. Aggregation of cartilage proteoglycans. 3. Characteristics of the proteins isolated from trypsin digests of aggregates. J Biol Chem. 1974. 249:4250–4256.
23. Hollander AP, Heathfield TF, Webber C, Iwata Y, Bourne R, Rorabeck C, Poole AR. Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. J Clin Invest. 1994. 93:1722–1732.
Article
24. Jacques C, Gosset M, Berenbaum F, Gabay C. The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation. Vitam Horm. 2006. 74:371–403.
Article
25. Johnson JA, Austin C, Breur GJ. Incidence of canine appendicular musculoskeletal disorders in 16 veterinary teaching hospitals from 1980 through 1989. Vet Comp Orth Traum. 1994. 7:56–59.
Article
26. Kaewsakorn T, Chotayaporn M, Suwankong N, Nganvongpanit K, Jitpean S, Cutesuwan P. Normal hematology and blood chemistry in small, medium and larged adult healthy dogs. Chiangmai Vet J. 2003. 1:35–49.
27. Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Altern Med Rev. 1998. 3:27–39.
28. Kiani C, Chen L, Wu YJ, Yee AJ, Yang BB. Structure and function of aggrecan. Cell Res. 2002. 12:19–32.
Article
29. Kikuchi T, Yamada H, Shimmei M. Effect of high molecular weight hyaluronan on cartilage degeneration in a rabbit model of osteoarthritis. Osteoarthritis Cartilage. 1996. 4:99–110.
Article
30. Knudson CB, Knudson W. Hyaluronan-binding proteins in development, tissue homeostasis, and disease. FASEB J. 1993. 7:1233–1241.
Article
31. Knudson W. The role of CD44 as a cell surface hyaluronan receptor during tumor invasion of connective tissue. Front Biosci. 1998. 1:d604–d615.
Article
32. Kongtawelert P, Ghosh P. An enzyme-linked immunosorbent-inhibition assay for quantiation of hyaluronan (hyaluronic acid) in biological fluids. Anal Biochem. 1989. 178:367–372.
Article
33. Leighton EA. Genetics of canine hip dysplasia. J Am Vet Med Assoc. 1997. 210:1474–1479.
34. Leipold HR, Goldberg RL, Lust G. Canine serum keratan sulfate and hyaluronate concentrations. Relationship to age and osteoarthritis. Arthritis Rheum. 1989. 32:312–321.
Article
35. Lohmander LS. Markers of cartilage metabolism in arthrosis. A review. Acta Orthop Scand. 1991. 62:623–632.
36. Lohmander LS, Dahlberg L, Eyre D, Lark M, Thonar EJ, Ryd L. Longitudinal and cross-sectional variability in markers of joint metabolism in patients with knee pain and articular cartilage abnormalities. Osteoarthritis Cartilage. 1998. 6:351–361.
Article
37. Lohmander LS, Ionescu M, Jugessur H, Poole AR. Changes in joint cartilage aggrecan after knee injury and in osteoarthritis. Arthritis Rheum. 1999. 42:534–544.
Article
38. Lust G. An overview of the pathogenesis of canine hip dysplasia. J Am Vet Med Assoc. 1997. 210:1443–1445.
39. Manicourt DH, Pita JC. Quantification and characterization of hyaluronic acid in different topographical areas of normal articular cartilage from dogs. Coll Relat Res. 1988. 8:39–47.
Article
40. Masuhara K, Nakai T, Yamaguchi K, Yamasaki S, Sasaguri Y. Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip. Arthritis Rheum. 2002. 46:2625–2631.
Article
41. May SA. Holton JEF, Collinson R, editors. Degenerative joint disease (osteoartritis), osteoartrosis, secondary joint disease. Manual of Small Animal Arthrology. 1994. Bournemounth, Cheltenham: British Small Animal Veterinary Association;62–74.
42. McLaughlin RM, Roush JK. Diagnosing osteoarthritis. Vet Med. 2002. 97:120–133.
43. Nganvongpanit K, Ong-Chai S. Biological marker for canine osteoarthritis diagnosis. Chiangmai Vet J. 2004. 2:39–49.
44. Okumura M, Tagami M, Fujinaga T. Measurement of serum and synovial fluid keratan sulphate and antibody to collagen type II in equine osteoarthritis. Zentralbl Veterinarmed A. 1998. 45:513–516.
Article
45. Owens JM, Biery DN. Radiographic Interpretation for the Small Animal Clinician. 1999. 2nd ed. Baltimore: Williams & Wilkins.
46. Paimela L, Heiskanen A, Kurki P, Helve T, Leirisalo-Repo M. Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthritis. Arthritis Rheum. 1991. 34:815–821.
Article
47. Peansukmanee S, Trinarong C, Kongtawelert P, Ongchai S. Chondroitin sulfate epitopes in sera of normal and osteoarthritic horses. Chiangmai Vet J. 2003. 1:3–10.
48. Petersson IF, Boegård T, Svensson B, Heinegård D, Saxne T. Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint. Br J Rheumatol. 1998. 37:46–50.
Article
49. Pothacharoen P, Siriaunkgul S, Ong-Chai S, Supabandhu J, Kumja P, Wanaphirak C, Sugahara K, Hardingham T, Kongtawelert P. Raised serum chondroitin sulfate epitope level in ovarian epithelial cancer. J Biochem. 2006. 140:517–524.
Article
50. Pothacharoen P, Teekachunhatean S, Louthrenoo W, Yingsung W, Ong-Chai S, Hardingham T, Kongtawelert P. Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and osteoarthritis patients. Osteoarthritis Cartilage. 2006. 14:299–301.
Article
51. Ratcliffe A, Beauvais PJ, Saed-Nejad F. Differential levels of synovial fluid aggrecan aggregate components in experimental osteoarthritis and joint disuse. J Orthop Res. 1994. 12:464–473.
Article
52. Ratcliffe A, Billingham MEJ, Saed-Nejad F, Muir H, Hardingham TE. Increased release of matrix components from articular cartilage in experimental canine osteoarthritis. J Orthop Res. 1992. 10:350–358.
Article
53. Rettenmaier JL, Keller GG, Lattimer JC, Corley EA, Ellersieck MR. Prevalence of canine hip dysplasia in a veterinary teaching hospital population. Vet Radiol Ultrasound. 2002. 43:313–318.
Article
54. Roush JK, McLaughlin RM, Radlinsky MAG. Understanding the pathophysiology of osteoarthritis. Vet Med. 2002. 97:108–119.
55. Sakugawa H, Nakayoshi T, Kobashigawa K, Yamashiro T, Maeshiro T, Miyagi S, Shiroma J, Toyama A, Nakayoshi T, Kinjo F, Saito A. Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2005. 11:255–259.
Article
56. Simánek V, Kren V, Ulrichová J, Gallo J. The efficacy of glucosamine and chondroitin sulfate in the treatment of osteoarthritis: Are these saccharides drugs or nutraceuticals? Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005. 149:51–56.
Article
57. Smedsrød B, Kjellén L, Pertoft H. Endocytosis and degradation of chondroitin sulphate by liver endothelial cells. Biochem J. 1985. 229:63–71.
Article
58. Smedsrød B, Pertoft H, Gustafson S, Laurent TC. Scavenger functions of the liver endothelial cell. Biochem J. 1990. 266:313–327.
Article
59. Smith GK, Mayhew PD, Kapatkin AS, Mckelvie PJ, Shofer FS, Gregor TP. Evaluation of risk factors for degenerative joint disease associated with hip dysplasia in German shepherd dogs, Golden retrievers, Labrador retrievers, and Rottweilers. J Am Vet Med Assoc. 2001. 219:1719–1724.
Article
60. Tangkijvanich P, Kongtawelert P, Pothacharoen P, Mahachai V, Suwangool P, Poovorawan Y. Serum hyaluronan: a marker of liver fibrosis in patients with chronic liver disease. Asian Pac J Allergy Immunol. 2003. 21:115–120.
61. Uesaka S, Nakayama Y, Shirai Y, Yoshihara K. Serum and synovial fluid levels of chondroitin sulfate in patients with osteoarthritis of the knee joint. J Nippon Med Sch. 2001. 68:165–170.
Article
62. Wight TN, Kinsella MG, Qwarnström EE. The role of proteoglycans in cell adhesion, migration and proliferation. Curr Opin Cell Biol. 1992. 4:793–801.
Article
63. Worrall JG, Wilkinson LS, Bayliss MT, Edwards JC. Zonal distribution of chondroitin-4-sulphate/dermatan sulphate and chondroitin-6-sulphate in normal and diseased human synovium. Ann Rheum Dis. 1994. 53:35–38.
Article
Full Text Links
  • JVS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr