Effect of TGF-beta(1) and Chitosan-TGF-beta(1) Conjugate on Collagenase Induced Arthritis of the Knee in Rabbits

PURPOSE; To evaluate the effects of the chitosan-TGF-beta(1) conjugate and TGF-beta(1) on osteoarthritic rabbit cartilage induced by collagenase type II. MATERIALS AND METHODS; Chemical arthritis was induced in right knee of 15 rabbits by injection of collagenase type II (4 mg/mL, 0.25 cc) twice at day 1 and 4, and then each 5 rabbits were treated by intra-articular injection of TGF-beta(1) (15 ng/mL, 1 mL, group I), chitosan-TGF-beta(1) conjugate (Chitosan: 5.8 g/mL, TGF-beta(1): 15 ng/mL, group II) and PBS (1 mL, group III) at 10 days later in the same knees. The appearance of the injected knee joints and lameness were observed weekly. The articular cartilage and synovium obtained at 4 weeks were analysed by gross findings (India ink), histological examinations (H&E, Safrainin O) and evaluation through the Kikuchi score. RESULT; The osteoarthritic sign about knee joints was the most severe at 1 weeks after the initiation of collagenase injections, but there wasere no difference of 3 groups in osteoarthritic sign and lameness was most severe in group 3. Group 2 showed the most superior results in gross findings using india ink and the these results were more prominent in the evaluation of histological scoring (average scores of each group I:14+/-2.7, II:10.3+/-1.2, III:20.3+/-3.7). CONCLUSION; These results might suggest that, in the rabbit osteoarthritic knee model induced by collagenase, Chitosan-TGF-beta(1) conjugate is more effective than only TGF-beta(1) in inhibiting cartilage degeneration.

The Effect of Chitosan-TGF-beta1 Conjugate on Full Thickness Articular Cartilage Defect in the Rabbit Knee Model (Preliminary Report) / 대한정형외과연구학회지

PURPOSE: To evaluate the effect of the chitosan-TGF-beta1 conjugate on articular cartilage defects of rabbits' knees MATERIALS AND METHODS: Full thickness cartilage defect(6mm, round shape) was made at both knees of 20 rabbits and, after the lapse of 3 days, chitosan-TGF-beta1(15ng/ml, 1ml) was injected into one side(experimental group) of knees and PBS(1ml) was injected into the other side(control group). 5 rabbits were sacrificed 6 weeks after the injection and the rest of 15 rabbits 12 weeks later. Then, gross morphology and histological evaluation(Mendelson scoring) was conducted. RESULTS: No arthritic findings was observed and histological results in the experimental group at 6(Ave. 11.3+/-1.5) and 12(Ave. 4.5+/-1.9) weeks postoperatively were superior to those in the control group at 6(Ave. 14.6+/-1.7) and 12(Ave. 9.8+/-2.2) weeks. Especially at 12 weeks, the experimental group was superior to the control group statistically in results of 5 subgroups except for filling of defects. The difference of two groups at 12 weeks was more remarkable than those at 6 weeks. CONCLUSION: Regeneration of something very close to normal cartilage was observed in the experimental group. It shows that the biological activity of TGF-beta1 is sustained by the action of conjugate with chitosan, through prolonged half life of TGF-beta1.