Effects And Mechanism Of Intraarticular Injection Of Doxycycline On Experimental Osteoarthritis In Rabbits

Objective: To investigate the effects and mechanism of intraarticular injection of doxycyline on experimental osreoarthritis in rabbits.Methods: Animal models of osteoarthritis in knee of rabbits had been established by intraarticular injection of 1.6% papain solution. 2 mg or 4 mg doxycycline were intraarticularly injected once a day in four weeks, subsequently detected the degeneration of articular cartilage, Mankin's marks of the cartilage tissue, MMP-13 expression, the release of nitricoxide (NO) and the activity of total nitricoxide synthase (NOS) and inducible nitricoxide synthase (iNOS) of the joint fluid.Results: In the osteoarthritis model, the Mankin's marks and the MMP-13 expression observably increased, spectrophotometric analysis showed high concentration NO release and high activity of NOS and iNOS in the joint fluid (P<0.01). The cartilage surface was irregular with an abundance of fissures visible in the naked eye, the wear and degeneration of cartilage including osteophytes were found. Injection of 0.2 mg/d doxycycline obviously decreased the Mankin's marks, the MMP-13 expression, the contents of NO and the activity of NOS and iNOS (P<0.01), 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 doxycycline more obviously strengthened the changes above.Conclusion: Intraarticular injection of doxycycline could delay the process of osteoarthritis, what's more, the effect is in relation to the dosage of the doxycycline: better effect followed greater dosage. The mechanism of action is relation to reduce NO release, alleviate total NOS and iNOS activity and MMP-13 expression.