Histological Changes In Articular Cartilage Research Articles

Regular walking exercise prior to knee osteoarthritis reduces joint pain in an animal model.

We investigated the effect of regular walking exercise prior to knee osteoarthritis (OA) on pain and synovitis in a rat monoiodoacetic acid (MIA)-induced knee OA model. Seventy-one male Wistar rats were divided into three groups: (i) Sedentary + OA, (ii) Exercise + OA, and (iii) Sedentary + Sham groups. The Exercise + OA group underwent a regular treadmill walking exercise at 10 m/min (60 min/day, 5 days/week) for 6 weeks, followed by a 2-mg MIA injection in the right knee. The right knee joint was removed from rats in this group at the end of the 6-week exercise period and at 1 and 6 weeks after the MIA injection. After the 6 weeks of treadmill exercise but before MIA injection, there were no significant differences among the three groups in the pressure pain threshold, whereas at 1 week post-injection, the Exercise + OA group's pressure pain threshold was significantly higher than that in the Sedentary + OA group, and this difference persisted until the end of the experimental period. The histological changes in articular cartilage and subchondral bone revealed by toluidine blue staining showed no difference between the Sedentary + OA and EX + OA groups. The expression levels of interleukin (IL)-4 and IL-10 mRNA in the infrapatellar fat pad and synovium were significantly increased by the treadmill exercise. Significant reductions in the number of CD68-, CD11c-positive cells and IL-1β mRNA expression and an increase in the number of CD206-positive cells were observed at 1 week after the MIA injection in the Exercise + OA group compared to the Sedentary + OA group. These results suggest that regular walking exercise prior to the development of OA could alleviate joint pain through increases in the expressions of anti-inflammatory cytokines in the rat infrapatellar fat pad and synovium.

Gumiganghwal-tang ameliorates cartilage destruction via inhibition of matrix metalloproteinase

Ethnopharmacological relevanceKyung-Bang Gumiganghwal-tang tablet (GMGHT) is a standardized Korean Medicine that could treat a cold, headache, arthralgia and fever. Although GMGHT has been used for arthritis-related diseases including a sprain, arthralgia, unspecified arthritis and knee arthritis, there is no pre-clinical evidence to treat osteoarthritis (OA). This study determined the drug dosage and the mechanisms of GMGHT for OA. MethodsOA was induced by intra-articular monoiodoacetic acid (MIA) injection in Sprague-Dawley rats. As calculated from the human equivalent dose formula, GMGHT was orally administered at the doses of 9.86, 98.6 and 986 mg/kg for 4 weeks. The arthritis score was performed by a blind test, and histological changes in articular cartilage were indicated by hematoxylin and eosin, Safranin O and toluidine blue staining. SW1353 chondrocytes were stimulated by interleukin (IL)-1β recombinant to analyze the expressions of Type II collagen, matrix metalloproteinases (MMPs) and nuclear factor (NF)-κB. ResultsRough and punctate surfaces of the femoral condyle induced by MIA, were recovered by the GMGHT treatment. The arthritis score was significantly improved in the 968 mg/kg of GMGHT-treated cartilage. Loss of chondrocytes and proteoglycan were ameliorated at the deep zone of the subchondral bone plate by the GMGHT administration in OA rats. The expression of Type II collagen was increased, while MMP-1, -3 and -13 levels were decreased in the GMGHT-treated SW1353 chondrocytes. In addition, the GMGHT treatment regulated NF-κB activation along with IL-6, transforming growth factor-β and IL-12 production. ConclusionsGMGHT promoted the recovery of articular cartilage damage by inhibiting MMPs, accompanied with its anti-inflammatory effects in OA. GMGHT might be an alternative therapeutic treatment for OA.

Disuse histological changes of an unloading environment on joint components in rat knee joints

To clarify the effects of mechanical unloading on joint components, including the articular cartilage by knee compartments, synovial membrane, and the infrapatellar fat pad (IFP), using a hindlimb suspension rat model. Twenty-five male rats were divided into the three following experimental groups: the baseline, control (CON), and hindlimb unloading (HU) groups. Rats in the HU group were subjected to periods of hindlimb unloading by tail suspension. The joint components were evaluated by histopathological and histomorphometric analyses. The unloading condition caused articular cartilage thinning and decreased matrix staining. The tendency of these histological changes in articular cartilage was similar between the knee compartments. In general, the unloading environment resulted in no critical histological changes to the synovial membrane and IFP. At 4 weeks, thickening of the synovial membrane and synovial-like tissue invasion were observed in the HU group, but there was no significant change in inflammation. There was no obvious histological change to the IFP caused by unloading. The unloading environment caused disuse histological changes in the articular cartilage; however, the tendency of the changes was similar between compartments. Furthermore, the unloading condition caused no critical histological changes to the synovial membrane or IFP. Clinically, the unloading environment without joint immobilization over a short period may not have caused critical histological changes to the joint components.

Induced lesion and inhibited Ihh-PTHrP signalling pathway activity in the articular cartilage of rats caused by T-2 toxin

This study aims to investigate the role of Ihh-PTHrP signalling pathway in the articular cartilage injury of rats caused by T-2 toxin. Sixty male Wistar rats were randomly divided into four groups: group A, normal diet; group B, normal diet plus the dissolvent (0.9% sodium chloride sterile aqueous solution containing ethanol); group C, normal diet plus low T-2 toxin (0.1 mg/kg BW/day) and group D, normal diet plus high T-2 toxin (0.2 mg/kg BW/day) by intragastric administration daily for 4 weeks. Histological changes in articular cartilage were assessed by HE staining and scanning electron microscopy. The expression of Ihh and PTHrP in cartilage was assessed by immunohistochemistry. There is a significant difference in average weight gain between group A and group D P < 0.01, groups A and D P < 0.001, respectively. The result of scanning electron microscopy and HE staining showed that the damage of articular cartilage was much severe with the increase of T-2 toxin. Immunohistochemical analysis indicated that the expression of Ihh in group A and group B was higher than that of group C and group D (P < 0.05, <0.01, respectively). However, the expression of PTHrP was lower in group A and group B than that of group C and group D (P < 0.001, <0.001, respectively). These results indicated that T-2 toxin can cause the damage to articular cartilage and weight loss in rats. The effect of T-2 toxin on articular cartilage of rat may be related to the Ihh-PTHrP pathway.

Combined detection of COMP and CS846 biomarkers in experimental rat osteoarthritis: a potential approach for assessment and diagnosis of osteoarthritis

BackgroundTo comprehensively evaluate the diagnostic value of serum cartilage oligomeric matrix protein (COMP) and chondroitin sulfate 846 epitope (CS846) biomarkers in osteoarthritis (OA), longitudinal and combined measurement of serum COMP and CS846 were performed at different stages in the pathological process of OA in a rat model of anterior cruciate ligament transection (ACLT).MethodsSixty male Sprague-Dawley rats were randomly divided into two groups, including a model group (n = 30) and a control group (n = 30). Rat models were established by ACLT surgery, and sham operations were performed on rats in the control group. Prior to surgery and at 2, 4, 6, 8, and 10 weeks after ACLT surgery, serum levels of COMP and CS846 biomarkers were determined using an enzyme-linked immunosorbent assay approach. Five rats per group were euthanized at 2, 4, 6, 8, and 10 weeks after surgery, after which tibial plateau specimens were collected. Macroscopic observation and histological examination were employed for rat tibial plateau. Histological changes in articular cartilage were evaluated according to Osteoarthritis Research Society International (OARSI) scoring criteria. The area under the curve (AUC) of COMP, CS846, and combined biomarkers was compared using receiver operating characteristic (ROC) curve.ResultsWithin 10 weeks after surgery, serum levels of COMP and CS846 in the model group were significantly higher when compared to those in the control group. Moreover, a significant correlation was observed between changes in COMP and CS846 levels. At each time point, macroscopic observations and OARSI scores were significantly increased in the development of OA. The AUC of combined biomarkers was higher compared to that of COMP and CS846 alone. Finally, a positive relationship was found between levels of COMP and CS846 and the OARSI score.ConclusionsIn this study, we found that combined detection of serum CS846 and COMP levels can be used for diagnosis and monitoring of OA progression.

Combined detection of serum CTX-II and COMP concentrations in osteoarthritis model rabbits: an effective technique for early diagnosis and estimation of disease severity.

BackgroundEarly diagnosis of osteoarthritis (OA) is difficult. Cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptides of type II collagen (CTX-II) are two markers which can potentially predict the destruction of articular cartilage of early OA. To comprehensively evaluate the diagnosis value of serum COMP and CTX-II markers in OA, the longitudinal and combined measurement of serum COMP and CTX-II were performed at different stages of pathological process of OA in adult rabbits with OA, compared with the sham-operated rabbits.MethodsThirty-six adult white rabbits were randomly divided into two groups, the OA group and the control group (n = 18 per group). OA models were established by anterior cruciate ligament transection. Sham operations were performed in the control group. Before the surgery and at weeks 2, 4, 6, 8, 10, and 12 after surgery, serum CTX-II and COMP concentrations were detected using sandwich-ELISA in all rabbits. Three rabbits in each group were killed at weeks 2, 4, 6, 8, 10, and 12 after surgery, and femoral condyle specimens were collected. Histological changes in articular cartilage were evaluated according to the Mankin scoring criteria.ResultsAt each time point, the Mankin scores and serum concentrations of CTX-II and COMP were significantly higher in the OA group than in the control group. In addition, in the OA group, there was a significant relationship between the CTX-II and COMP concentrations and the Mankin score.ConclusionsEarly dynamic combined detection of serum CTX-II and COMP concentrations is effective for early OA diagnosis and evaluation of OA severity.

Preventive effects of hyaluronan from deterioration of gait parameters in surgically induced mice osteoarthritic knee model

Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk. Histological evaluation was performed to assess articular cartilage changes in the knee joints. Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.

The effects of high molecular weight hyaluronic acid (Hylan G-F 20) on experimentally induced temporomandibular joint osteoartrosis: part II

The aim of this study was to determine the efficacy of Hylan G-F 20 on experimentally induced osteoarthritic changes in rabbit temporomandibular joint (TMJ). A 3 mg/ml concentration of sodium mono iodoacetate (MIA) had been injected into both joints of 24 rabbits to create osteoartrosis. The study group was injected with Hylan G-F 20 in one joint and saline in the contralateral joint as a control (once a week for 3 weeks). Histological changes in articular cartilage, osteochondral junction, chondrocyte appearance and subchondral bone were determined at 4, 6, and 8 weeks. Regarding cartilage, there was a statistically significant difference between the two groups at 4 weeks. Degenerative bony changes to subchondral bone were significantly higher in the controls. No statistical difference was found in the study group at 6 weeks. A positive correlation was found between osteochondral junction and subchondral bone in the study group at 8 weeks. The changes in chondrocyte appearance were significantly decreased in the study group at all follow-up times. Intra-articular injection of Hylan G-F 20 decreased cartilage changes in early stage TMJ osteoartrosis and clustering of chondrocytes showed the chondroprotective effects of Hylan G-F 20 caused by hypertrophic responses.

A cadaveric investigation into the links between macroscopic and microscopic osteoarthritic changes at the hip

Our objective was to investigate the frequency and distribution of osteoarthritic changes at the hip, including the relationship between osteoarthritic lesions on the femoral head surface and histological changes in articular cartilage, in 12 cadavers. Twelve embalmed cadavers (five males and seven females) were dissected, and the femoral head was removed from both sides (24 femoral heads). Any gross osteoarthritic changes were noted and graded (on a scale of 1-3). A circular disc was then removed from the equator of the femoral head and divided into nine regions. Out of 192 segments, 54 underwent sectioning and staining with haematoxylin and eosin to assess histological changes in cartilage. Osteoarthritis of the hip was present in all cadavers, with all males having bilateral OA and 50% having grade 2 or higher lesions (50% were grade 1), and four of the seven female specimens having bilateral OA and only 7% with grade 2 lesions (with 71% grade 1 and 21% normal). Chondrocyte clustering was most commonly observed in the deep layer of cartilage followed by the intermediate and superficial layers respectively, as the grade of the macroscopic lesion increased. Cartilage injury at the histological level precedes any visible denudation of the femoral head articular cartilage. This study supports the hypothesis that early osteoarthritic changes occur in the deep layer of cartilage near the tide mark and progress superficially concomitant with an overall increase in the osteoarthritic lesion size on the femoral head surface.