[Long-term effect of nitric oxide synthase inhibitor on repair of articular cartilage defects repairing].
OBJECTIVE
To discuss the long-term effect of inducible nitric oxide synthase inhibitor S-methylisothiourea (SMT) on repair of articular cartilage defects.


METHODS
Twenty-four adult New Zealand White rabbits with full-thickness defects of cartilage created in the trochlear groove of their bilateral femurs were divided into three groups randomly, 8 in each group: (1) control group in which nothing was filled into the defects; (2) BMP group in which the defects were filled with collagen fibrin gel impregnated with recombinant human bone morphogenic protein (rhBMP); and (3) SMT group in which the defects were filled with collagen fibrin gel impregnated with rhBMP and hypodermic injection of SMT (5 mg .(-1) 12 h(-1)) was given. The animals were killed one year later. The gross appearance of the defects was assessed. The amount of released NO and the activity of NOS were examined by chemical colorimetry. The distribution of collagen was examined by immunohistochemistry. The proteoglycan synthesis and cell activity was assessed by incorporation of radiolabelled sodium sulphate Na(2)(35)SO(4) and bromodeoxyuridine.


RESULTS
One year after the defects in SMT group showed greater improvement in margin integration, cellular morphology, and architecture within defect than those in BMP group and control group (P < 0.01). Immunohistochemistry showed that there was less type-I collagen and more type-II collagen in SMT group than in the other two groups. Radiolabelled sodium sulphate (Na(2)(35)SO(4)) incorporation test showed that the proteoglycan synthesis in defects was higher in SMT group than in the other two groups (P < 0.01). BrdU incorporation test showed cells in repaired tissue with remarkable proliferous activity.


CONCLUSIONS
iNOS inhibitor SMT significantly improves the quality of repair of defected cartilage and delays its degradation.
Sun
Wei
W
Department of Orthopaedics Surgery, Nanfang Hospital Affiliated to First Militery Medical University, Guangzhou 510515, China.
Wang
Jixing
J
Jin
Dadi
D
Liu
Xiaoxia
X
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D007592:Joint Diseases / Q000188:drug therapy* / Q000473:pathology; D007596:Joints / Q000187:drug effects / Q000293:injuries; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D013462:Sulfur Radioisotopes
D000963:Antimetabolites; D004791:Enzyme Inhibitors; D013462:Sulfur Radioisotopes; D007550:Isothiuronium; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C027744:S-methylisothiopseudouronium; D001973:Bromodeoxyuridine