The effects of doxycycline on the mRNA expressions of MMP-3 and TIMP-1 of articular cartilage and synovial membrane in osteoarthritis / 中国医师杂志

ABSTRACT

Objective To investigate the mechanisms regarding protection of doxycycline from articular cartilage cataplasis in osteoarthritis,and provide experimental evidence for prevention and cure of degenerative osteoarthropathy and for treatment of osteoarthritis.Methods (Ⅰ) ModelsSixteen New Zealand rabbits underwent right anterior cruciate ligament riesction,and fed in each cage.The animals were injected with penicillin 400 thousands IU once a day for 3 days to prevent from infection.On the fourth day after operation,the animals were compelled to use their operated knee by driving 60 minutes per day for 4 weeks.(2) Animal groupsthe animals were divided into two groups.The animals in experimental group were injected into the knees with 1.33％ doxycycline 0.3 ml (total 0.4 mg),once a day for 4 weeks.Rabbits in the control group were treated under the same condition using normal saline 0.3 ml.All rabbits were fed in their own cage and not drove.The total time was 4 weeks.(3)Example collection and data analysis:Rabbits were sacrificed by aeroembolism and their knee joints were examined by gross morphology.The mRNA expressions of MMP-3 and TIMP-1 in the cartilage and synovium were analyzed by a reverse transcription polymerase chain reaction ( RT - PCR).Results For the experimental group,condyles of femur cartilage inspection revealed that 6 cases were in Grade 0 and 2 cases were in Grade 1,and whirbone cartilage inspection showed that 5 cases were in Grade 0 and 3 cases were in Grade 1.For the control group,2 cases were in Grade 0 and 6 cases were in Grade 1.The extent of articular cartilage cataplasis was significantly different mRNA expression of MMP-3 ( 1.20 ± 0.32) (experimental) and ( 1.97 ± 0.54) (compared) ( t =3.47,P＜ 0.05).The expression of MMP-3 mRNA in cartilage and synovium was significantly decreased,respectively; while the expression of TIMP-1 mRNA was significantly increased in the experimental group(3.22 ±0.42) compared to the control group( 1.90 ±0.33) ( t =6.99,P ＜ 0.01 ).Conclusions Intra-articular injections of doxycycline inhibits the articular cartilage and synovial MMP-3 mRNA expression and increases TIMP-1 mRNA expression,thereby reducing the extent of degeneration of articular cartilage.