Abstract: AIM: To investigate the effects and mechanisms of intraarticular injection of doxycycline on experimental osreoarthritis in rabbits. METHODS: An animal model of osteoarthritis in knee of rabbits was es-tablished by intraarticular injection of papain. 2 mg or 4 mg of doxycycline was injected (intraarticular) once a day in four weeks. The degeneration of articular cartilage, Mankin's marks of the cartilage tissue,the expression of MMP-13, the release of nitricoxide (NO) and the activity of total nitricoxide synthase (NOS) and inducible nitri-coxide synthase (iNOS) of the joint fluid were tested sub-sequently.RESULTS: In the osteoarthritis model group, the Mankin,s marks and the expression of MMP-13 ob-servably increased, and spectrophotometric analysis showed the high concentration of the release of NO and high activity of NOS and iNOS in the joint fluid (P < 0.01). The cartilage surface was irregular with an abun-dance of fissures visibly by the naked eye, and the wear and degeneration of cartilage including osteophytes were found. Injection of 0.2 mg·d¹ doxycycline obviously de-creased the Mankind marks, the expression of MMP-13, the contents of NO and the activity of NOS and iNOS (P <0.01), and it alleviated the wear and degeneration of cartilage including the fissures and the formation of the osteophyte in the same time. Injection of 0.4 mg·d^-1 doxycycline more obviously strengthened the changes above. CONCLUSION: Intraarticular injection of doxy-cycline can delay the process of osteoarthritis, and the ef-fect is related to the dosage of the doxycycline: better ef-fect followed larger dosage. The mechanisms are related to inhibiting the level of NO, the activity of total NOS and iNOS activity and the expression of MMP-13.

Key words: osteoarthritis, doxycycline, NO, NOS, MMP-13, therapy