417 ALFA-PINENE PREVENTS INTERLEUKIN-1BETA-INDUCED NF-KAPPAB ACTIVATION AND NITRIC OXIDE PRODUCTION IN HUMAN CHONDROCYTES

Abstract

has been implicated in AC-100 mechanism of action. As ondontoblasts and osteoblasts are from the same mesenchymal stem cell lineage as chondroblasts, an osteochondral defect model was chosen for a pilot study to investigate the activity of AC-100 on cartilage repair. The goat is well accepted for use in cartilage repair studies due to the comparable stifle joint size and cartilage thickness to humans. Methods: Fifteen skeletally mature female Spanish goats were used to evaluate the healing response of an osteochondral femoral condylar defect filled with a collagen sponge+AC-100 or +saline. In each goat, a single full thickness (approximately 6 mm in diameter, 6 mm deep) cylindrical defect was created in the anterior medial femoral condyle of the right hind leg stifle joint. A cylindrical plug cut from a collagen sponge (CollaPlug; 6mm diameter, 6mm long) was implanted into the lesion site. The collagen sponge was saturated with the test article (saline; AC100 2.5, 25mg/application). Post-operative treatments included intra-articular injections (0.5mL) of the appropriate test article into the operated knee joint at 1, 2 and 3 weeks post surgery. On day 84 (12 weeks) after surgery, two animals from each group, and on day 168 (24 weeks), three animals from each group were humanely euthanized. The joints were grossly evaluated for specific changes relative to the medial femoral condyle and the contacting surfaces. The operated femoral condyle was analyzed by histology. Results: There was good correlation between the gross evaluation and the quantitative histological evaluation. The normalized gross evaluation of the repair tissues showed AC-100 high dose group to have better healing outcomes (score 2.9, p=0.056 vs. saline group) than the saline control group (score 0) and the low dose AC-100 group (score 0.7). At 24 weeks, the high dose AC-100 group exhibited a better gross outcome (score 6.3), than the saline control (score 4.0) and low dose AC-100 (score 5.5) groups. At 12 weeks, the histological evaluation score (max. 28) of the MFC lesions in the high dose AC-100 group had slightly better healing outcomes (score 13.5) than the saline control (score 9.0) and low dose AC-100 (score 10.0) groups, agreeing with the gross observation scoring. At 24 weeks, the MFC lesions in the high dose AC-100 group exhibited better outcomes (score 20.3) than the saline control (score 17.5) and low dose AC-100 (score 15.7) groups. There was no evidence of an inflammatory response in any sections examined. Conclusions: This pilot study showed a clear trend for AC-100 to promote repair of an osteochondral defect. A larger more comprehensive study will be required to establish the optimum dosing regimen.