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Table 4 Summary of in vivo results using the MMT/MCLT rat model

From: Randomized controlled studies on the efficacy of antiarthritic agents in inhibiting cartilage degeneration and pain associated with progression of osteoarthritis in the rat

  MMT/MCLT model Results
  Trial 1: systemic delivery (n = 8) Weight bearing (significant effects; h; p < 0.05) Histopathology (n = 8)
  Drug (daily) Dose Route (1 ml.) 7 days 14 days 21 days Cartilage degeneration score Total joint score
1 Saline control n.a. i.p.     1.83 ± 0.31 12.29 ± 0.62
2 Morphine 10 mg/kg i.p. 1 1,3,5 3,5 2.33 ± 0.66 12.96 ± 0.89
3 Tacrolimus 0.3 mg/kg i.p. 3 0,1,3,5,24 3 0.5 ± 0.15a 7.13 ± 0.69b
4 Tacrolimus 0.6 mg/kg i.p. 1 0.96 ± 0.27c 6.96 ± 0.65b
5 Fluocinolone 0.005 mg/kg i.p. 5 1,3 1 1.33 ± 0.14 10.75 ± 0.61
6 Fluocinolone 0.010 mg/kg i.p. 1, 24 1,3,5,24 1.96 ± 0.77 10.54 ± 0.88
7 Clonidine 0.100 mg/kg i.p. 1 1,3,5 3,5,24 1.29 ± 0.20 11.33 ± 0.55
8 Alendronate 10 μg/kg i.p. 5 1 1.79 ± 0.60 11.55 ± 0.72
9 Curcumin 50 mg/kg p.o. 0,1,3,5,24 0, 3 2.21 ± 0.60 12.96 ± 0.62
10 Withaferin 50 mg/kg p.o. 1 3 1.83 ± 0.52 11.83 ± 0.61
  Trial 2: intraarticular delivery (n = 10) Weight bearing (significant effects) Histopathology (n = 10)
  Drug (weekly) Dose Route (30 μl) 7 days 14 days 21 days Synovium Cartilage degeneration score Total joint score
1 Saline control n.a. i.a.    1.07 ± 0.24 10.23 ± 0.85
2 Clonidine 100 μg/kg s.c. +/− +/− +/− +/− 0.77 ± 0.28 11.03 ± 0.61
3 Clonidine 4.5 μg i.a. 0.67 ± 0.23 9.13 ± 0.54
4 Triamcinolone H 0.15 mg i.a. + 2.03 ± 0.52 11.30 ± 1.21
5 Tacrolimus 15 ng i.a. 0.87 ± 0.36 8.60 ± 0.63
6 Tacrolimus 30 ng i.a. 0.8 ± 0.19 8.90 ± 0.66
7 Fluocinolone 15 ng i.a. 0.8 ± 0.25 9.80 ± 0.51
8 Curcumin 30 μg i.a. 1.63 ± 0.61 9.57 ± 0.91
  1. n.a. not applicable, i.a. intraarticular, s.c. subcutaneous, MMT/MCLT medial meniscal tear/medial collateral ligament tear. −24 = worse at 24 h; “Pretrt” refers to an effect on pain that is measurable before dosing
  2. The details of the related studies and results are provided in Additional file 1. In trial 1, drug administration was prophylactic in that test articles were administered subcutaneously daily for 3 weeks beginning 1 day before surgery. In trial 2, drug administration was therapeutic in that drugs were administered weekly beginning 1 week after surgery. For weight bearing, shown are hours after drug delivery when a statistically measurable effect (p ≤ 0.05) was observed compared with the pretreatment baseline of that day, unless noted otherwise. With regard to histopathological measurements, medial femur cartilage degeneration and total joint score are noted. The scores approach 0 with improvement. The mean osteophyte score for each joint was added to the total cartilage degeneration score to create a total joint score. Additional measures of tibial cartilage, bone and synovial changes as well as details of statistical analysis are provided in Additional file 1
  3. a p ≤ 0.005 compared with vehicle alone
  4. b p ≤ 0.001 compared with vehicle alone
  5. c p ≤ 0.05 compared with vehicle alone