1. Peterson KD, Keefe TJ. Effects of meloxicam on severity of lameness and other clinical signs of osteoarthritis in dogs. J Am Vet Med Assoc 2004; 225:1056–1060.
2. Benton HP, Vasseur PB, Broderick-Villa GA, et al. Effect of carprofen on sulfated glycosaminoglycan metabolism, protein synthesis, and prostaglandin release by cultured osteoarthritic canine chondrocytes. Am J Vet Res 1997; 58:286–292.
3. Dvorak LD, Cook JL, Kreeger JM, et al. Effects of carprofen and dexamethasone on canine chondrocytes in a three-dimensional culture model of osteoarthritis. Am J Vet Res 2002; 63:1363–1369.
4. Collier S, Ghosh P. Comparison of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on proteoglycan synthesis by articular cartilage explant and chondrocyte monolayer cultures. Biochem Pharmacol 1991; 41:1375–1384.
5. Ghosh P. Nonsteroidal anti-inflammatory drugs and chondro-protection. A review of the evidence. Drugs 1993; 46:834–846.
6. Henrotin Y, Bassleer C, Reginster JY, et al. Effects of etodolac on human chondrocytes cultivated in three dimensional culture. Clin Rheumatol 1989; 8(suppl 1):36–42.
7. Rainsford KD, Ying C, Smith FC. Effects of meloxicam, compared with other NSAIDs, on cartilage proteoglycan metabolism, synovial prostaglandin E2, and production of interleukins 1, 6 and 8, in human and porcine explants in organ culture. J Pharm Pharmacol 1997; 49:991–998.
8. Redini F, Mauviel A, Loyau G, et al. Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. II: glycosaminoglycan synthesis. Agents Actions 1990; 31:358–367.
9. Wilbrink B, Van der Veen MJ, Huber J, et al. In vitro influence of ketoprofen on the proteoglycan metabolism of human normal and osteoarthritis cartilage. Agents Actions 1991; 32:154–159.
10. Palmoski MJ, Brandt KD. Proteoglycan depletion, rather than fibrillation, determines the effects of salicylate and indomethacin on osteoarthritic cartilage. Arthritis Rheum 1985; 28:548–553.
11. Palmoski MJ, Brandt KD. Aspirin aggravates the degeneration of canine joint caused by immobilization. Arthritis Rheum 1982; 25:1333–1342.
12. Manicourt DH, Druetz-Van Egeren A, Haazen L, et al. Effects of temoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage. Br J Pharmacol 1994; 113:1113–1120.
13. Bassleer C, Magotteaux J, Geenen V, et al. Effects of meloxicam compared to acetylsalicylic acid in human articular chondrocytes. Pharmacology 1997; 54:49–56.
14. Blot L, Marcelis A, Devogelaer JP, et al. Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage. Br J Pharmacol 2000; 131:1413–1421.
15. Giannoni P, Crovace A, Malpeli M, et al. Species variability in the differentiation potential of in vitro-expanded articular chondrocytes restricts predictive studies on cartilage repair using animal models. Tissue Eng 2005; 11:237–248.
16. Webber RJ, Malemud CJ, Sokoloff L. Species differences in cell culture of mammalian articular chondrocytes. Calcif Tissue Res 1977; 23:61–66.
17. Jovanovic DV, Fernandes JC, Martel-Pelletier J, et al. In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: suppression of collagenase 1 and interleukin-1beta synthesis. Arthritis Rheum 2001; 44:2320–2330.
18. Mastbergen SC, Marijnissen AC, Vianen ME, et al. Inhibition of COX-2 by celecoxib in the canine groove model of osteoarthritis. Rheumatology (Oxford) 2006; 45:405–413.
19. Pelletier JP, Boileau C, Boily M, et al. The protective effect of licofelone on experimental osteoarthritis is correlated with the downregulation of gene expression and protein synthesis of several major cartilage catabolic factors: MMP-13, cathepsin K and aggrecanases. Arthritis Res Ther 2005; 7:R1091–R1102.
20. Pelletier JP, Lajeunesse D, Jovanovic DV, et al. Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis. J Rheumatol 2000; 27:2893–2902.
21. Ding C. Do NSAIDs affect the progression of osteoarthritis? Inflammation 2002; 26:139–142.
22. Beluche LA, Bertone AL, Anderson DE, et al. Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism. Am J Vet Res 2001;62:1916–1921.
23. Yuan Y, Chen XY, Wei XY, et al. Pharmacokinetic studies of meloxicam following oral and transdermal administration in Beagle dogs. Acta Pharmacol Sin 2009; 30:1060–1064.
24. Stoker AM, Cook JL, Kuroki K, et al. Site-specific analysis of gene expression in early osteoarthritis using the Pond-Nuki model in dogs. J Orthop Surg Res [serial online]. 2006; 1:8. Available at: www.josr-online.com/content/1/1/8. Accessed Oct 10, 2006.
25. Farndale RW, Buttle DJ, Barret AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883:173–177.
26. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 1996; 29:225–229.
27. Chadwick RB, Conrad MP, McGinnis MD, et al. Heterozygote and mutation detection by direct automated fluorescent DNA sequencing using a mutant Taq DNA polymerase. Biotechniques 1996; 20:676–683.
28. Matyas JR, Atley L, Ionescu M, et al. Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis. Arthritis Rheum 2004; 50:543–552.
29. Hanks BC, Kuroki K, Stoker AM, et al. Evaluation of anti-inflammatory and chondroprotective effects of peroxisome proliferator-activated receptor gamma agonists in cartilage and synovial explants from dogs. Am J Vet Res 2010; 71:1142–1147.
30. Breshears LA, Cook JL, Stoker AM, et al. Detection and evaluation of matrix metalloproteinases involved in cruciate ligament disease in dogs using multiplex bead technology. Vet Surg 2010; 39:306–314.
31. Alvarez-Soria MA, Herrero-Beaumont G, Sánchez-Pernaute O, et al. Diacerein has a weak effect on the catabolic pathway of human osteoarthritis synovial fibroblast: comparison to its effects on osteoarthritic chondrocytes. Rheumatology 2008; 47:627–633.
32. Goldring MB, Berenbaum F. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clin Orthop Relat Res 2004;(suppl 427):S37–S46.
33. Hardy MM, Seibert K, Manning PT, et al. Cyclooxygenase 2-dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants. Arthritis Rheum 2002; 46:1789–1803.
34. Martel-Pelletier J, Pelletier J, Fahmi H. Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum 2003; 33:155–167.
35. Kühn K, D'Lima DD, Hashimoto S, et al. Cell death in cartilage—review. Osteoarthritis Cartilage 2004; 12:1–16.
36. Amin AR, Attur M, Patel RN, et al. Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide. J Clin Invest 1997; 99:1231–1237.
37. Jeon JE, Schrobback K, Hutmacher DW, et al. Dynamic compression improves biosynthesis of human zonal chondrocytes from osteoarthritis patients. Osteoarthritis Cartilage 2012; 20:906–915.
38. Hogrefe C, Joos H, Maheswaran V, et al. Single impact cartilage trauma and TNF-α: interactive effects do not increase early cell death and indicate the need for bi-multidirectional therapeutic approaches. Int J Mol Med 2012; 30:1225–1232.
39. Huskisson EC, Berry H, Gishen P, et al. Effects of antiinflammatory drugs on the progression of osteoarthritis of the knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal Antiinflammatory Drugs in Knee Osteoarthritis. J Rheumatol 1995; 22:1941–1946.
Advertisement
Objective—To assess effects of in vitro meloxicam exposure on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis
Sample—Femoral head cartilage from 16 dogs undergoing total hip replacement
Procedures—Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG, chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1β, tumor necrosis factor-α, cyclooxygenase-1, cyclooxygenase-2, and nducible nitric oxide synthase gene expression were evaluated. Comparisons between tissues cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and 30.0 μg/mL for up to 30 days were performed by means of repeated-measures analysis.
Results—Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA concentrations. Expression of ADAMTS-5 was significantly decreased in all groups on all days, compared with the day 0 value. On day 3, culture medium PGE2 concentrations were significantly lower in all meloxicam-treated groups, compared with values for controls, and values remained low. Culture medium MMP-3 concentrations were significantly lower on day 30 than on day 3 in all meloxicam-treated groups.
Conclusions and Clinical Relevance—Results suggested that in vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days did not induce matrix degradation or stimulate MMP production. Meloxicam lowered PGE2 release from this tissue, and effects on tissue chondrocyte content and matrix composition were neutral.
Supported in part by a grant from Boehringer Ingelheim Vetmedica Inc.
Presented in part as an abstract at the Annual Osteoarthritis Research Society International World Congress, San Diego, September 2011.