Effect of nitric oxide synthase inhibitor on proteoglycan metabolism in repaired articular cartilage in rabbits.
OBJECTIVE
To study the effect of nitric oxide synthase inhibitor, S-methyl thiocarbamate (SMT), on proteoglycan metabolism in repaired articular cartilage in rabbits.


METHODS
Twenty-four male New Zealand white rabbits, aged 8 months and weighing 2.5 kg+/-0.2 kg, were used in this study. Cartilage defects in full thickness were created on the intercondylar articular surface of bilateral femurs of all the rabbits. Then the rabbits were randomly divided into 3 groups (n=8 in each group). The defects in one group were filled with fibrin glue impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2, BMP group), in one group with fibrin glue impregnated with rhBMP-2 and hypodermic injection with SMT (SMT group) and in the other group with nothing (control group). All the animals were killed at one year postoperatively. The tissue sections were stained with safranine O-fast green and analyzed by Quantiment 500 system to determine the content of glycosaminoglycan through measuring the percentage of safranine O-stained area, the thickness of cartilages and the mean gray scale (average stain intensity). Radiolabelled sodium sulphate (Na(2)(35)SO(4)) was used to assess the proteoglycan synthesis.


RESULTS
At one year postoperatively, the percentage of safranine O-stained area, the mean gray scale and the cartilage thickness of the repaired tissues in SMT group were significantly higher than those of BMP group (P<0.01) and the control group (P<0.05). Result of incorporation of Na(2)(35)SO(4) showed that the proteoglycan synthesis in SMT group was higher than those of BMP group and the control group (P<0.01).


CONCLUSIONS
SMT, a nitric oxide synthase inhibitor, can significantly increase the content of glycosaminoglycan and proteoglycan synthesis, and computer-based image analysis is a reliable method for evaluating proteoglycan metabolism.
Sun
Wei
W
Department of Traumatic Surgery, Shenzhen Second People's Hospital, Shenzhen 518025, China. yjdsw@yahoo.com
Jin
Da-di
DD
Wang
Ji-xing
JX
Qin
Li-yun
LY
Liu
Xiao-xia
XX
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002357:Cartilage Diseases / Q000188:drug therapy / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011336:Probability; D011509:Proteoglycans / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity
D011509:Proteoglycans; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium