Repair effect of articular cartilage defects by nitric oxide synthase inhibitor

Objective To discuss repairing effects of articular cartilage defects by nitric oxide synthase inhibitor (S methylisothiourea, SMT), and explore the role of nitric oxide in cartilage repair. Methods Full-thickness defects of cartilage were created in the intercondylar trochlear groove of femur of thirty-six adult New Zealand white rabbits, and were divided into three gorups. Twenty-four defects were untreated as the control, twenty-four were filled with fibrin glue and impregnated with rhBMP AS rhBMP group, the rest twenty-four were filled with fibrin glue and impregnated with rhBMP, and hypodermic injection with SMT as SMT group. The animals were sacrified at sixteen weeks postoperatively, and the gross appearance of the defect was estimated. The repair tissue was examined histologically and was evaluated according to the grading scale of histology. The amount of released NO and the activities of nitric oxide synthase(NOS) were examined by chemical colorimetry. The distribution of type-Ⅰ , Ⅱ

Objective To discuss repairing effects of articular cartilage defects by nitric oxide synthase inhibitor (S methylisothiourea, SMT), and explore the role of nitric oxide in cartilage repair. Methods Full-thickness defects of cartilage were created in the intercondylar trochlear groove of femur of thirty-six adult New Zealand white rabbits, and were divided into three gorups. Twenty-four defects were untreated as the control, twenty-four were filled with fibrin glue and impregnated with rhBMP AS rhBMP group, the rest twenty-four were filled with fibrin glue and impregnated with rhBMP, and hypodermic injection with SMT as SMT group. The animals were sacrified at sixteen weeks postoperatively, and the gross appearance of the defect was estimated. The repair tissue was examined histologically and was evaluated according to the grading scale of histology. The amount of released NO and the activities of nitric oxide synthase(NOS) were examined by chemical colorimetry. The distribution of type-Ⅰ , Ⅱ collagen were examined by Sirius-Red. The proteoglycan synthesis was assessed by incorporation of radio-labelled sodium sulphate Na35 SO42-. RT - PCR examined the expression of iNOS mRNA and MMP9 mRNA. Results The filled extent of the defect in SMT group and rhBMP group had no significant difference from the control group, and the marginal integration, cellular morphology, architecture within the defect and subchondral plate repair were better than the untreated defects ( P < 0.05) according to the histological score. Sirius-Red stain demonstrated less significant type-1 collagen in the defects treated with rhBMP and SMT than in the untreated defects,and more type-Ⅱ collagen than in untreated defects. NoO release(24.97 ±3.95 )μmol/L and NOS activity( 1.17± 0.31) U/ml in SMT group were less than rhBMP and the control(F = 21.287,F= 15.932,P < 0.05 ). Incorporation of isotope 35S was more significant in SMT(48 276 ±5 791.58)cpm than in rhBMP(37 624 ±5 217.34)cpm and the control(10 285 ± 867.5)cpm (P<0.05). MMP9 mRNA expressed in all of the groups, but less in SMT than the control(t = 4.29,P<0.05), and no iNOS mRNA expression was found in SMT group. Conclusion iNOS inhibitor could improve the quality of articular cartilage repair tissues. 11 refs,7 figs,2 tabs.