Veterinary Research Forum
Vet Res Forum

Tibial plateau levelling osteotomy: significance of matrix metalloproteinases in long-term monitoring of canine stifle stabilization after cranial cruciate ligament rupture

Document Type : Original Article

Authors

Dragan Jevrem Ristanović 1
Jelena Vladimir Francuski Andrić 2
Milena Danilo Radaković 2
Kristina Adam Spariosu 2
Ivan Željko Vlahek 3
Marija Tomo Lipar 4
Petar Sreten Milosavljević 1
Mario Ivan Kreszinger 4

1 Department of Surgery, Faculty of Veterinary Medicine, Orthopedics and Ophthalmology, University of Belgrade, Belgrade, Serbia

2 Department of Pathophysiology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia

3 Department of Animal Breeding and Livestock, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia

4 Department of Surgery, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia

https://doi.org/10.30466/vrf.2023.2017099.4089
Abstract
Cranial cruciate ligament rupture is one of the most common causes of osteoarthritis in dogs. Surgical stabilization is obligatory and tibial plateau levelling osteotomy (TPLO) is the most commonly used surgical technique. Studies on the long-term monitoring of matrix metallo-proteinases (MMPs) and acute-phase proteins are limited, especially those with parallel monitoring of changes in the serum, synovial fluid (SF) and urine. We aimed to describe long-term changes in 1) MMPs: gelatinases and caseinases, 2) APPs: ceruloplasmin, haptoglobin and paraoxonase-1, and 3) the correlation of MMPs in the serum, SF and urine with lameness in dogs 2 and 6 months undergoing TPLO. From 17 dogs diagnosed with cranial cruciate ligament rupture, sera, SF and urine samples were collected preoperative 2 and 6 months after the surgery. Relative activity (RA) of MMPs was measured in all samples using zymography. Acute-phase proteins were measured in the serum and SF using spectrophotometry and agarose gel electrophoresis. Relative activity of MMPs in serum was not change at different sampling points. In SF, a marked decrease in MMPs RA was evident, however, only RA of caseinases was significantly reduced during the recovery period. In urine, RA of caseinases was positively correlated with the lameness score with decreasing activity trend during time. Serum and synovial acute-phase proteins were not changed after surgery, which was consistent with the agarose gel analyses. Decreased activity of caseinases pointed to reduced degradation of extracellular matrix after TPLO. Synovial and urine caseinases are potential biomarkers in predicting the recovery outcome following stifle stabilization.

Keywords

Acute phase proteins
Caseinases
Dogs
Gelatinases
Urine

Subjects

  1. Nečas A, Zatloukal J, Kecová H, et al. Predisposition of dog breeds to rupture of the cranial cruciate ligament. Acta Vet Brno 2000; 69(4): 305-310.
  2. Gordon-Evans WJ, Griffon DJ, Bubb C, et al. Comparison of lateral fabellar suture and tibial plateau leveling osteotomy techniques for treatment of dogs with cranial cruciate ligament disease. J Am Vet Med Assoc 2013; 243(5): 675-680.
  3. Nelson SA, Krotscheck U, Rawlinson J, et al. Long-term functional outcome of tibial plateau leveling osteotomy versus extracapsular repair in a heterogeneous population of dogs. Vet Surg 2013; 42(1): 38-50.
  4. Kjelgaard-Hansen M, Christensen MB, Lee MH, et al. Serum amyloid A isoforms in serum and synovial fluid from spontaneously diseased dogs with joint diseases or other conditions. Vet Immunol Immunopathol 2007; 117(3-4): 296-301.
  5. Boal S, Miguel Carreira L. Serum and synovial fluid C-reactive protein level variations in dogs with degenerative joint disease and their relationships with physiological parameters. Vet Res Commun 2015; 39(3): 163-169.
  6. Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int J Mol Sci 2020; 21(24): 9739. doi: 10.3390/ijms21249739.
  7. Mustafa S, Koran S, AlOmair L. Insights into the role of matrix metalloproteinases in cancer and its various therapeutic aspects: a review. Front Mol Biosci 2022; 9: 896099. doi: 10.3389/fmolb.2022.896099.
  8. Muir P, Danova NA, Argyle DJ, et al. Collagenolytic protease expression in cranial cruciate ligament and stifle synovial fluid in dogs with cranial cruciate ligament rupture. Vet Surg 2005; 34(5): 482-490.
  9. Fujita Y, Hara Y, Nezu Y, et al. Proinflammatory cytokine activities, matrix metalloproteinase‐3 activity, and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture. Vet Surg 2006; 35(4): 369-376.
  10. Alves JC, Santos A, Jorge P, et al. The influence of IL-1 and C-reactive protein levels in synovial fluid of companion dogs with bilateral hip osteoarthritis on various clinical disease parameters. Am J Vet Res 2022; 83(11): 1-10.
  11. Löfqvist K, Kjelgaard-Hansen M, Nielsen MBM. Usefulness of C-reactive protein and serum amyloid A in early detection of postoperative infectious complications to tibial plateau leveling osteotomy in dogs. Acta Vet Scand 2018; 60(1): 30. doi: 10.1186/s13028-018-0385-5.
  12. Fujita Y, Hara Y, Nezu Y, et al. Biomarkers in dogs surgically treated for ruptured cranial cruciate ligaments. Vet Rec 2012; 171(17): 426. doi: 10.1136/vr.100801.
  13. Coulson A, Lewis N. An Atlas of interpretative radiographic anatomy of the dog and cat. 2nd Iowa, USA: Blackwell Publishing 2008; 78-83.
  14. Slocum B, Slocum TD. Tibial plateau levelling osteotomy for repair of cranial cruciate ligament rupture in the canine. Vet Clin North Am Small Anim Pract 1993; 23(4): 777-795.
  15. Spariosu K, Janjić F, Radaković M, et al. Low serum levels of promatrix metalloproteinase-2 and -9 occur during acute Babesia canis infection in dogs. Vet Parasitol 2021; 300: 109612. doi: 10.1016/j.vetpar. 2021.109612.
  16. Milanović Z, Ilić A, Andrić JF, et al. Acute-phase response in Babesia canis and Dirofilaria immitis co-infections in dogs. Ticks Tick Borne Dis 2017; 8(6): 907-914.
  17. Sunderman FW Jr, Nomoto S. Measurement of human serum ceruloplasmin by its p-phenylenediamine oxidase activity. Clin Chem 1970; 16(11): 903-910.
  18. Owen JA, Better FC, Hoban J. A simple method for the determination of serum haptoglobins. J Clin Pathol 1960; 13(2): 163-164.
  19. Dantoine TF, Debord J, Charmes JP, et al. Decrease of serum paraoxonase activity in chronic renal failure. J Am Soc Nephrol 1998; 9(11): 2082-2088.
  20. Gautreaux MA, Tucker LJ, Person XJ, et al. Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models. J Orthop Res 2022; 40(6): 1251-1262.
  21. Markus DH, Hurley ET, Mojica ES, et al. Concentration of synovial fluid biomarkers on the day of anterior cruciate ligament (ACL)-reconstruction predict size and depth of cartilage lesions on 5-year follow-up. Knee Surg Sports Traumatol Arthrosc 2023; 31(5): 1753-1760.
  22. Schmidt EMS, Rubio CP, Thomas F, et al. Acute phase proteins in bitches subjected to conventional and minimally invasive ovariohysterectomy. Pesq Vet Bras 2018; 38(11): 2124-2128.
  23. Shahid M, Manchi G, Brunnberg L, et al. Use of proteomic analysis to determine the protein constituents of synovial fluid samples from the stifle joints of dogs with and without osteoarthritis secondary to cranial cruciate ligament rupture. Am J Vet Res 2018; 79(4): 397-403.
  24. Evans-Pickett A, Longobardi L, Spang JT, et al. Synovial fluid concentrations of matrix metalloproteinase-3 and interluekin-6 following anterior cruciate ligament injury associate with gait biomechanics 6 months following reconstruction. Osteoarthritis Cartilage 2021; 29(7): 1006-1019.
  25. Garner BC, Stoker AM, Kuroki K, et al. Using animal models in osteoarthritis biomarker research. J Knee Surg 2011; 24(4): 251-264.
  26. Volk SW, Kapatkin AS, Haskins ME, et al. Gelatinase activity in synovial fluid and synovium obtained from healthy and osteoarthritic joints of dogs. Am J Vet Res 2003; 64(10): 1225-1233.
  27. Rabillard M, Danger R, Doran IP, et al. Matrix metalloproteinase activity in stifle synovial fluid of cranial cruciate ligament deficient dogs and effect of postoperative doxycycline treatment. Vet J 2012; 193(1): 271-273.
  28. Malek S, Weng HY, Martinson SA, et al. Evaluation of serum MMP-2 and MMP-3, synovial fluid IL-8, MCP-1, and KC concentrations as biomarkers of stifle osteo-arthritis associated with naturally occurring cranial cruciate ligament rupture in dogs. PloS One 2020; 15 (11): e0242614. doi: 10.1371/journal.pone.0242614.
  29. Vandooren J, Itoh Y. Alpha-2-macroglobulin in inflammation, immunity and infections. Front Immunol 2021; 12: 803244. doi: 10.3389/fimmu.2021.803244.
  30. Bay-Jensen AC, Mobasheri A, Thudium CS, et al. Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers. Curr Opin Rheumatol 2022; 34(1): 54-60.
  31. Wigner NA, Kulkarni N, Yakavonis M, et al. Urine matrix metalloproteinases (MMPs) as biomarkers for the progression of fracture healing. Injury 2012; 43(3): 274-278.
Veterinary Research Forum
Volume 16, Issue 2
February 2025
Pages 63-69

  • Receive Date 04 December 2023
  • Revise Date 22 August 2024
  • Accept Date 24 December 2023

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