| Articular cartilage is the important part of the synovial joints, its main function is conducting the distribution of sports load, maintain and withstand the contact stress and the successful completion of joint function activities. Various bone and joint diseases such as cancer and bone trauma can lead to cartilage defects. Articular cartilage has a special structure, it does not contain nerve, blood vessels, lymphatics. Besides, juvenile articular cartilage obtained nutrition by passage of the subchondral, but adult articular cartilage without subchondral nutrition passage, so it has a limited repair capacity, once damaged, it always results in arthritis, what impacts the joint function. Thus the repair of articular cartilage defects has been become highly concerned by the medical professions at home and abroad, and become the urgent problem that needs solve.There are many kinds of treatment to cartilage defects, such as drug therapy, biological therapy, surgical methods, cartilage tissue engineering and so on. With the development of biomedical, biological therapy attracted more and more attention. The research of chondrocytes transplantation, cytokines transplantation, tissue-engineered cartilage and other methods has been develop quickly, but currently mostly limited to basic research, clinical research and application is not yet mature, and its long-term efficacy remains to be further clarified. Surgical procedures, including microfracture surgery, autologous chondrocyte transplantation, allograft, periosteum and cartilage grafting, have been reported that made gratifying effects, but the repaired tissue is far less than normal cartilage structure, and the biomechanical properties falls far, as well as a serious lack of natural function, and, over time, these organizations began to emerge degeneration, eventually leading to loss of joint function. Therefore, how to improve the quality of articular cartilage defect repair catches more and more attention from researchers.Adult articular cartilage has no subchondral nutrition pathways, nutrient supply is produced by pressure changes during joint activities which lead to synovial fluid exchange between the joint cavity and the cartilage matrix. Many experiments show that static can lead to degeneration of articular cartilage, but its mechanism occurs not only with joint activities, but also closely related to the weight-bearing of joints. Some scholars have proposed two hypotheses:(1)"cartilage pump" mechanism. The nutritional pathway not only needs joint activities, but also requires a certain amount of stress, lack of adequate stress, even keep joint movement, cartilage is still not effective access to nutrition.(2) there is some cartilage stress sensing means in chondrocytes, to maintain the normal physiological activity of cartilage, chondrocytes need a certain amount of stress stimuli. When joint be fixed, intra-articular stress anomalies, in addition to the occlusal surface static stress sustained presence, the rest of the cartilage surface lacking stress stimuli, sustained low stress itself can lead to cartilage degeneration.It is generally believed that the normal physiological function of chondrocytes is closely related to normal stress stimulation, exercise can improve the quality of cartilage repair. Static and increased joint loading can leading articular cartilage degeneration. Exercise can promote the repair of full-thickness cartilage defects. Chondrocytes are sensitive to mechanical stimulation, steady pressure can inhibit the synthesis of cartilage matrix proteins, and periodic changes in pressure can stimulate its synthesis. So joints movement is vital to cartilage nutrition supply. Pressure on joints and cartilage caused by alternating pressure to form the so-called "cartilage pump" cartilage nutrition mechanism. Exercise can reduce intra-articular pressure in favor of synovial fluid to the cartilage surface and diffuse interstitial cells provide the best environment to cartilage repair and promoting the repair process. Scholars have studied the effects of exercise on the knee cartilage, most results showed that exercise is beneficial to cartilage repair, but there are also some studies have shown that movement does not promote cartilage repair. We carefully read these documents and found that there are differences among the researches about exercise intensity, exercise timing, exercise intensity criteria and other aspects, which are probably ultimately lead to different findings, the effects of different intensity of exercise and different intervention time for repair of cartilage defects has not yet been reported.Synthesis of chondrocytes and secretion of cartilage matrix precursor material is regulated to some extent by the normal physiological process, chondrocytes occurs synthesis and secretion of matrix decline in the absence of sufficient stress stimulation. Full-thickness cartilage defect repair mechanisms are:bleeding from subchondral bone to defect region leading to hematoma formation, while the bottom of the base of cancellous bone contains mesenchymal stem cells which have a variety of proliferation functions. The hematoma containing red blood cells, white blood cells and undifferentiated cellulose cells. The clot develops to granulation tissue, then fibrocartilage, hyaline cartilage, finally converted to the cartilage. Small full-thickness cartilage defect repair contains several stages:after two days there are mesenchymal stem cells ingrowth in the defect region, four weeks appeared fibrocartilage in the defect, hyaline cartilage appears at eight weeks, at12weeks the repair tissue began to degenerate. Many studies focus on the effects of passive movement on cartilage defect repair, fewer research the effects of active movement on cartilage repair. Our experiment made a rat knee trochlear full thickness cartilage defect model, different timing and different intensity treadmill exercise was conducted to the rats, in order to observe the effects of exercise on rat knee full thickness cartilage defect repair remodeling, to provide experimental basis for clinical cartilage treatment and rehabilitation.The experiment consists of three parts, the first part discusses the influence of different intensity treadmill exercise on early repair of rat knee cartilage full-thickness defects, and to explore the mechanisms of repair; the second part will explore the influence of different exercise intervention time on repair of rat knee full-thickness cartilage defect; the third part discusses the impact of different intensity treadmill exercise on repair and remodeling of rat full-thickness articular cartilage defect.Part One:Effects of treadmill exercise on early repair of cartilage full-thickness defects on rat kneePurpose:The aim of chaptor one was to investigate the effects of different intensities of exercise on early repair of patellofemoral full-thickness articular cartilage defects of rat, investigate the serum MMP-3, TIMP-1expression.Materials and methods:1. Modeling:A full-thickness cartilage defect model with lmm in diameter was made in the rat knee patellofemoral articular surface of the distal femur, and2mm from the intercondylar fossa. Rats were randomly divided into sedentary group (SED), low-intensity exercise group (LIR), intensity exercise group (MIR) and high-intensity exercise group (HIR).2. Treadmill exercise intervention:Low, medium and high intensity exercise group were conducted corresponding intensity treadmill exercise respectively one week after the modeling. Low-intensity treadmill exercise is incline0°, speed8.2m/min; moderate-intensity treadmill exercise of slope5°, speed15.2m/min; high-intensity treadmill exercise treadmill slope of10°, speed of26.7m/min; each exercise group exercise daily40min, training Monday to Friday, Saturdays and Sundays with no exercise. Rats in sedentary group were rearing in cage, and they can move freely in the cage.3. Index detection:Generally observed; tissue sections stained; O’Driscoll score; assay blood MMP-3, TIMP1-concentration and TIMP-1/MMP-3ratio by ELISA.Results:Macroscopic view and tissue sections staining showed that defects in SED group repaired best, and the repair tissue contains more matrix; O’Driscoll scores showed the highest score was in SED group, each exercise group were lower than the SED group, and high-intensity exercise group scored the lowest; ELISA results showed that blood MMP-3, TIMP-1concentration were related to intensity of movement, the higher exercise intensity, the higher the content of MMP-3, while the lower TIMP-1levels, and TIMP-1/MMP-3is consistent with the degree of cartilage repair.Conclusion:This part of the experiment confirmed that low, medium and high intensity exercise inhibited early repair of patellofemoral full-thickness cartilage defects in rats, high-intensity exercise further damage to the subchondral bone. MMP-3and TIMP-1expression was associated with exercise intensity, and the value of TIMP-1/MMP-3ratio was consistent with the degree of cartilage repair. And further study about the effects of different exercise timings and intensities on the repair of full-thickness cartilage defect was worth. Part Two:Effect of treadmill exercise timing on repair of full-thickness defects of articular cartilagePurpose:The aim of chaptor two was to investigate the effects of different of treadmill exercise timing on repair of full-thickness defects of articular cartilage, to provide experimental evidence for the clinical weight-bearing and exercise timing after treatment for cartilage damage.Materials and methods:1. Modeling:A full-thickness cartilage defect model with1mm in diameter was made in the rat knee patellofemoral articular surface of the distal femur, and2mm from the intercondylar fossa. Rats were randomly divided into sedentary group (SED), two weeks after modeling exercise group (2W), four weeks after modeling exercise group (4W) and eight weeks after modeling exercise group (8W).2. Treadmill exercise intervention:Rats were rearing in cage after modeling.2W group,4W group,8W group were conducted moderate-intensity treadmill exercise after2weeks,4weeks,8weeks after modeling respectively. The moderate-intensity was defined as:the slope of5°, speed15.2m/min, sports40min a day, training from Monday to Friday, Saturdays and Sundays without exercise. Rats in sedentary group were rearing in cage, and they can move freely in the cage.3. Index detection:Generally observed; tissue sections stained; O’Driscoll score; Immunohistochemical determination of type II collagen content in repair tissue; qPCR determination collagen II and glycoside polysaccharide content in repair tissue.Results:General concept and staining tissue sections showed that defects in4W group repaired best, and the repair tissue contains more matrix; O’Driscoll scores showed the highest score was in4W group, and the lowest score appeared in2W group. Immunohistochemistry showed that the highest collagen type II content of repair tissue was in4W group, the lowest was in2W group. qPCR results showed that the highest GAG and collagen Ⅱ content was in4W group, and the minimum content appeared in2W group, the difference was statistically significant.Conclusion:The results show that at the right time moderate-intensity exercise can promote cartilage defect repair, improve the quality of repair tissue and shorten the repair time; premature movement will not be able to promote the repair of cartilage defects, but also for cartilage repair negative impact on the process; rather limited role is to delay the movement of cartilage repair. This study provides an experimental basis the clinical treatment of patients with cartilage defects and rehabilitation, but there is a long way to go from experiments to clinical, and the long-term effects of exercise on cartilage repair mechanism needs further study.Part Three:Experimental study of effect of different intensity treadmill exercise on rat full-thickness cartilage defect repairPurpose:The aim of chaptor three was to investigate the effects of different intensity of treadmill exercise on repair of full-thickness defects of articular cartilage, to provide experimental evidence for the clinical weight-bearing and exercise timing after treatment for cartilage damage.Materials and methods:1. Modeling:A full-thickness cartilage defect model with lmm in diameter was made in the rat knee patellofemoral articular surface of the distal femur, and2mm from the intercondylar fossa. Rats were randomly divided into sedentary group (SED), low-intensity exercise group (LIR), intensity exercise group (MIR) and high-intensity exercise group (HIR).2. Treadmill exercise intervention:Low, medium and high intensity exercise group were conducted corresponding intensity treadmill exercise respectively four weeks after the modeling. Low-intensity treadmill exercise is incline0°, speed8.2m/min; moderate-intensity treadmill exercise of slope5°, speed15.2m/min; high-intensity treadmill exercise treadmill slope of10°, speed of26.7m/min; each exercise group exercise daily40min, training Monday to Friday, Saturdays and Sundays with no exercise. Rats in sedentary group were rearing in cage, and they can move freely in the cage.3. Index detection:Generally observed; tissue sections stained; O’Driscoll score; Immunohistochemical determination of type II collagen content in repair tissue; qPCR determination collagen II, glycoside polysaccharide, BMP and GIF content in repair tissue.Results:General concept and staining tissue sections showed that defects in MIR group repaired best, and the repair tissue contains more matrix; O’Driscoll scores showed the highest score was in MIR group, and the lowest score appeared in HIR group. qPCR results showed that the highest collagen II, glycoside polysaccharide, BMP and GIF content was in MIR group, and the minimum content appeared in HIR group, the difference was statistically significant.Conclusion:The results of this section indicate that moderate mild treadmill exercise can promote the repair of full-thickness articular cartilage defects in rats, low intensity exercise for full thickness articular cartilage defects in rats has limited role in the promotion of full-thickness articular cartilage repair, and high-intensity treadmill exercise has damaging effects. Mechanisms of full-thickness articular cartilage defect was promoted by movement maybe the joint movement increased the content of IGF and BMP, thus contributing to bone mesenchamal stem cells into cartilage cells, cartilage cells and promotes the secretion of matrix and eventually promoted cartilage defect repair. |
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