Recovery Of Articular Cartilage Research Articles

다양한 운동 강도가 골관절염 흰쥐의 관절 연골 회복에 미치는 영향

PURPOSE: This study examined the effects of exercise of diverse intensities on the recovery of articular cartilage in osteoarthritic rats. METHODS: Over a period of four weeks, the authors applied treadmill exercise programs of diverse intensities to Sprague-Dawley rats, to which intra-articular injection of monosodium iodoacetate(MIA, 3mg/<TEX>$50{\mu}l$</TEX>, diluted in saline) was applied to the right knee joint to induce osteoarthritis. The four-week exercise program was not carried out with the control group(CG, n=10). Exercise programs of applicable intensities were applied to the low-intensity exercise group(LEG, n=10), moderate-intensity exercise group(MEG, n=10), and high-intensity exercise group(HEG, n=10) over the four weeks. Observations were made of morphological changes in the rats' articular cartilage, using hematoxylin and eosin stains. RESULTS: there were significant differences(p<.05) in the comparison of articular damage scores between the four groups involved. Articular cartilage damage scores were found to be significantly lower in the LEG, MEG, and HEG than in the CG, indicating that exercise helped with the recovery of cartilage. Of these latter three groups, the MEG showed the highest level of recovery, while the HEG showed the lowest. CONCLUSION: These study results suggest that exercise is effective in treating OA. They also indicate that in prescribing exercise to treat osteoarthritic patients, exercise of moderate intensity is most suitable to patients' physical conditions, rather than low or high intensity, maximizes, and so should be used to maximize the effects of therapy.

Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes

Articular chondrocytes proliferate in monolayer culture, but the expression of the transcription factor SOX9 falls and the ability of the cells to reform cartilage tissue declines. We have investigated whether retroviral SOX9 expression in extensively passaged human articular chondrocytes from osteoarthritic (OA) joints enables the cells to regain a cartilage matrix forming phenotype in pellet culture. Chondrocytes from normal and OA joints were retrovirally transduced with SOX9 and grown to passages 7-10 before being cultured as pellets of 500,000 cells for 14 days. Pellets were analysed by real time polymerase chain reaction, histology, immunohistochemistry and 1,9-dimethylmethylene blue assay. Chondrocytes from OA joints displayed higher expression of COL2A1 gene when transduced with SOX9 and cultured as pellets with 10% serum, but glycosaminoglycan (GAG) synthesis was low. Addition of transforming growth factor beta-3 and insulin like growth factor-1 increased collagen II expression and GAG synthesis in these SOX9 transduced cell pellets. The cells adopted a rounded morphology and there was increased deposition of collagen II protein compared to control green fluorescent protein transduced cell pellets. Similar results were seen with transduced chondrocytes from OA or healthy cartilage. SOX9 transduced human dermal fibroblasts did not show any chondrogenic response. Transduction with SOX9 primed the passaged articular chondrocytes to regain a chondrocytic phenotype in pellet culture and to form a cartilaginous matrix, which was enhanced by growth factors. Following transduction, chondrocytes from OA joints showed a similar capacity for chondrogenic recovery as those from healthy joints, which suggested that OA does not permanently compromise the chondrocyte phenotype.

Remobilization Does Not Fully Restore Immobilization Induced Articular Cartilage Atrophy

The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage.

The recovery of articular cartilage in explant culture from interleukin-1α: Effects on proteoglycan synthesis and degradation

The cytokine interleukin-1 (IL-1) strongly inhibits proteoglycan biosynthesis and increases extracellular proteoglycan degradation in cartilage. In this study we investigated how quickly proteoglycan turnover recovered after IL-1 treatment. Porcine articular cartilage in explant culture was incubated with recombinant human (rh) IL-1 alpha, rh insulin-like growth factor (IGF)-1 or rh-transforming growth factor (TGF)-beta 1 for 3 days. RhIL-1 alpha strongly inhibited synthesis and promoted matrix degradation over 3 days, whereas rhIGF-1 stimulated proteoglycan synthesis, and rhTGF-beta 1 had no significant effect on synthesis. In the absence of serum, the recovery of proteoglycan synthesis after IL-1 treatment (10 ng/ml) for 3 days was extremely slow, and it remained 30% inhibited even after a further 8 days of recovery. Matrix degradation of proteoglycan assessed from the rate of release of glycosaminoglycan into the culture medium recovered more quickly and was greatly reduced within 3 days. Shorter exposure of explants to IL-1 alpha (8 h) resulted in less inhibition of synthesis, but it did not result in a more rapid rate of recovery following its removal. Treatment of cartilage with IGF-1 (20 ng/ml) or TGF-beta (10 ng/ml) during the recovery period increased the rate of recovery of both synthesis and degradation. Synthesis recovered to control rates within 6 days and degradation within 2 days. TGF-beta (10 ng/ml) was slightly more potent than IGF-1. Fetal calf serum (10% v/v) also promoted recovery in a similar way to the growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Articular cartilage thickness and glycosaminoglycan distribution in the young canine knee joint after remobilization of the immobilized limb

The recovery of articular cartilage from atrophy induced by joint immobilization was investigated in immature dogs. In a previous study, we showed that 11 weeks of immobilization of the knee (stifle) joint of young dogs reduced the concentration of articular cartilage glycosaminoglycans (GAGs) by 13-47%. In the present study, right hindlimbs from six female beagles were immobilized for 11 weeks, as in the previous study, and then were remobilized for 15 weeks. Cartilage from the knee joint was compared with cartilage from nonimmobilized knees of eight age-matched control beagles. Histological samples taken from 11 different locations of the knee joint were stained with safranin O, and microspectrophotometry was used to demonstrate distribution of GAGs in the tissue. After remobilization, GAG concentration was restored in the patellofemoral region and tibial condyles. On the summits of the femoral condyles, and especially at the periphery of the femoral condyles, GAG concentration remained 8-26% less than the control values. On the summits, the thickness of the uncalcified cartilage was as much as 15% less than in the age-matched controls. Consequently, the changes induced by unloading were reversible to a great extent, but a full restoration of articular cartilage was not obtained at all sites of the knee joint within the 15 weeks of remobilization. Immobilization of the skeletally immature joint therefore may affect the development of articular cartilage in such a way that very slow recovery or permanent alterations are induced.

Lubrication of Animal Joints

The arthrotripsometer is an apparatus for sensing and recording the instantaneous frictional properties and deformations of articular cartilage in vitro under conditions simulating human locomotion. The frictional force measurements would have been straightforward were it not that the center of rotation of the twenty-one canine ankles studied varied throughout each oscillation. Folding of the friction-force curves about the end points of oscillation served to determine the instantaneous center of rotation and coefficient of friction. The center of rotation was determined as the mid-point between the two curves in the central portion of travel and extrapolated to the trailing end of each oscillation. At the start of each half cycle of oscillation, there occurred an abrupt transition and then a slower buildup of the coefficient of friction. These end effects are attributed to both shearing and small compressive deformations (plowing) of the articular cartilage. The plowing component of sliding friction decreased with increasing speed. The coefficient of friction decreased with increasing load. The friction was much lower in joints than in metallic or rubber bearings. When immersed in physiological saline solution, the mean sliding coefficient of friction of the ankles was .0124 (fifty-seven tests); whereas, bovine synovial fluid reduced this value by an additional 54 per cent to µ = .0057 (nineteen tests). The recovery of articular cartilage from compressive deformation was much quicker when the joint was oscillated than when it was stationary.