| ObjectiveKnee osteoarthritis(KOA)is a kind of chronic and progressive osteoarthropathy,including genetic,metabolic,developmental,stress imbalance,trauma,endocrine and other biological and mechanical factors that interact with each other and eventually lead to knee joint cartilage degeneration,subchondral bone sclerosis,subchondral bone cyst and osteophyte formation.Relevant data show that its incidence is increasing year by year and tends to be younger.Appropriate exercise can improve the development of knee osteoarthritis,but high intensity exercise can cause traumatic knee arthritis in mice.In recent years,traumatic knee osteoarthritis is in a high incidence state.The ideal way of building to its complex pathogenesis research plays a vital role,therefore,the experimental design will respectively for 8 and 20 weeks mice treadmill exercise and meniscus instability(destabilization of the medial meniscus,DMM)surgical traumatic knee osteoarthritis model is set up,and carries on the comparison to the effect,the mechanism of action and for subsequent movement rehabilitation effect of study provides a feasible and efficient and repeatable way of building.MethodsThirty-two male C57BL/6 mice aged 8 weeks and 20 weeks were randomly divided into control group(n=8),operation group(n=8),sham group(n=8)and exercise group(n=8).Control group without any intervention,routine feeding;DMM surgery was performed on the bilateral knee joints of mice in the operation group.In the sham group,only the joint capsule was opened in both knees.The exercise group received five-week running table training.The first week was exercise adaptation week,60 minutes each time,and the speed gradually increased from 0 m/s to 16m/min in a week.Back around for weeks,time of 80 minutes every time,10 minutes to prepare activities speed starting from 6 m/min speed increases gradually at a speed of 1 m/min to 16 m/min,constant speed in a 60 minutes to keep 16 m/min,10 minutes of relaxation velocity from 16m/min to 1 m/min speed decreased to 0 m/min.Draw materials within 48 hours after training.Gross observation was made on the knee joints of each group.The content of inflammatory cytokines in blood was detected by ELISA.RT-qPCR was used to detect mRNA levels of inflammatory factors in knee cartilage.All results were expressed as mean standard deviation(X SD)and analyzed using SPSS 20.0 software.Univariate anova was used within the group,and Bonferrori method was used between the groups for comparison.Results(1)The influence of modeling method and week-old age on body weight of mice: During the four-week running exercise and the four-week DMM surgery,the body weight of the 8-week-old mice presented A growing trend,but the body weight of the intervention showed A small increase at week 1and 2,and A slight increase at week 3 and 4.The body weight of20-week-old mice decreased in the first week,but then showed an overall upward trend.The body weight of mice in the NOR group showed a continuous upward trend,and the body weight of DMM group,SHAM group and RUN group was lower than that of the NOR group,with statistical difference(*P<0.05,**P<0.01 vs NOR).(2)The influence of modeling mode and age on the tissue morphology of the knee joint: both treadmill exercise and DMM surgery resulted in irregular cracks on the surface of the cartilage of the knee joint in mice,with disordered arrangement of chondrocytes and a reduced number of chondrocytes.Compared with the normal group,there was a significant difference between the DMM group and the SHAM group.Among them,the DMM group of 8-week-old mice was more severely damaged than the RUN group,and there was a significant difference.The chondrocytes in both the DMM group and the RUN group of 20-week-old mice showed decreased cell number and disordered arrangement,but there was no significant difference.Compared with the normal group,the running table movement caused the destruction of tide line and cartilage calcification.Compared with SHAM group,DMM surgery also presented the phenomenon of tidal line destruction and cartilage calcification,and the DMM group was more serious than the RUN group,with significant differences.(3)The effect of modeling method and age on the mRNA level of inflammatory factors in the knee cartilage of mice: DMM surgery and running table intervention aggravated the damage of type ii collagen fiber in the articular cartilage,and the mRNA level of Collagen2 in 20-week-old mice was lower than that of 8-week-old mice,but there was no significant difference.TNF-mRNA levels of pro-inflammatory cytokines were significantly higher in the treadmill exercise group than in the normal group,and significantly higher in the DMM surgery group than in the SHAM group.The mrna level of pro-inflammatory cytokine mmp9 was significantly higher in the treadmill exercise group than in the normal group,and significantly higher in the DMM surgery group than in the SHAM group,and significantly higher in the RUN group than in the DMM group at 8 weeks of age.The levels of pro-inflammatory cytokine il-6 mrna were significantly higher in the running table group than in the normal group,and significantly higher in the DMM operation group than in the SHAM group,and significantly higher in the RUN group than in the DMM group at 8 weeks and 20 weeks of age.(4)The effect of modeling method and week age on the expression of glucosaminoglycan in the blood of mice: the serum level of glucosaminoglycan in the DMM operation group was also lower than that in the DMM operation group *P<0.05 vs NOR.The contents of mice at 20 weeks were lower than those in the RUN group and the DMM group,but there was no significant difference.ConclusionBoth running table exercise and DMM surgery can cause knee cartilage injury in C57BL/6 mice and induce KOA,which proves thatrunning table exercise can be used as a model construction method for studying the mechanism of KOA in mice.Running on the treadmill can cause KOA in both young and middle-aged mice,thus providing an exercise model construction scheme for the study on the mechanism of KOA in young and middle-aged mice. |
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