Degree Of Cartilage Degradation Research Articles

Medial meniscal ossicles: Associated knee MRI findings in a multicenter case-control study

PurposeThe purpose of this study was to assess and compare the prevalence of meniscal, ligament and cartilage lesions on knee MRI in a series of age- and sex-matched patients with and without medial meniscal ossicle. Materials and methodsForty-two knee MRI examinations obtained in 42 patients (36 men, 6 women; mean age, 42.5±22.2 [SD] years; range: 19–65years) on which a medial meniscal ossicle was present were compared to 42 knee MRI examinations obtained in 42 age- and sex-matched patients (36 men, 6 women; mean age, 41.8±20.6 [SD] years; range: 19–65years) on which no medial meniscal ossicles were present. Two radiologists (R1, R2) blinded to the presence of meniscal ossicle by reading only the fat-saturated intermediate-weighted MR images separately assessed the presence of meniscal, ligament and cartilage lesions on these 84 knee MRI examinations. Prevalence of meniscal and ligament lesions and degree of cartilage degradation at MRI were compared between knees with and those without medial meniscal ossicle. ResultsIn knees with medial meniscal ossicle, R1 and R2 detected 33 (79%) and 38 (90%) medial meniscal lesions, respectively that involved the posterior root (n=25/32 for R1/R2), the posterior horn (n=19/14 for R1/R2) or the body (n=8/10 for R1/R2). The prevalence of posterior root tear (60% [25/42]/76% [32/42] for R1/R2) and that of anterior cruciate ligament (ACL) lesions (48% [20/42]/57% [24/42] for R1/R2) as well as the medial cartilage degradation score (3.35±0.87 [SD] for R1 and 3.92±0.78 [SD] for R2) were significantly greater in knees with than in knees without medial meniscal ossicle (root lesions: P<0.01 for both readers; ACL lesions and medial cartilage score: P<0.01 for both readers). ConclusionOn MRI examination, knees with a medial meniscal ossicle demonstrate a greater frequency of medial posterior root tear and of ACL lesions and a greater degree of medial femoro-tibial cartilage degradation by comparison with knees without medial ossicle.

Endoglin haploinsufficiency is associated with differential regulation of extracellular matrix production during skin fibrosis and cartilage repair in mice.

Transforming growth factor (TGF)-β is a multifunctional growth factor with potent pro-fibrotic effects. Endoglin is a TGF-β co-receptor that strongly regulates TGF-β signaling in a variety of cell types. Although aberrant regulation of TGF-β signaling is known to play a key role in fibrotic diseases such as scleroderma and impaired cartilage repair, the significance of endoglin function in regulating these processes is poorly understood. Here we examined whether endoglin haploinsufficiency regulates extracellular (ECM) protein expression and fibrotic responses during bleomycin induced skin fibrosis and surgically induced osteoarthritis, using endoglin-heterozygous (Eng+/-) mice and wild-type (Eng+/+) littermates. Skin fibrosis was induced by injecting mice intradermally with bleomycin or vehicle. Osteoarthritis was induced surgically by destabilization of medial meniscus. Dermal thickness, cartilage integrity and ECM protein expression were then determined. Eng+/- mice subjected to bleomycin challenge show a marked decrease in dermal thickness (P < 0.005) and reduced collagen content and decreased collagen I, fibronectin, alpha-smooth muscle actin levels as compared to Eng+/+ mice, both under basal and bleomycin treated conditions. Eng+/- mice undergoing surgically induced osteoarthritis show no differences in the degree of cartilage degradation, as compared to Eng+/+ mice, although chondrocytes isolated from Eng+/- display markedly enhanced collagen II levels. Our findings suggest that endoglin haploinsufficiency in mice ameliorates bleomycin-induced skin fibrosis suggesting that endoglin represents a pro-fibrotic factor in the mouse skin. However, endoglin haploinsufficiency does not protect these mice from surgically indicedcartilage degradation, demonstrating differential regulation of endoglin action during skin and cartilage repair.

MiR‐370 and miR‐373 regulate the pathogenesis of osteoarthritis by modulating one‐carbon metabolism via SHMT‐2 and MECP‐2, respectively

The aim of this study was to determine the mechanism underlying the association between one-carbon metabolism and DNA methylation during chronic degenerative joint disorder, osteoarthritis (OA). Articular chondrocytes were isolated from human OA cartilage and normal cartilage biopsied, and the degree of cartilage degradation was determined by safranin O staining. We found that the expression levels of SHMT-2 and MECP-2 were increased in OA chondrocytes, and 3′UTR reporter assays showed that SHMT-2 and MECP-2 are the direct targets of miR-370 and miR-373, respectively, in human articular chondrocytes. Our experiments showed that miR-370 and miR-373 levels were significantly lower in OA chondrocytes compared to normal chondrocytes. Overexpression of miR-370 or miR-373, or knockdown of SHMT-2 or MECP-2 reduced both MMP-13 expression and apoptotic cell death in cultured OA chondrocytes. In vivo, we found that introduction of miR-370 or miR-373 into the cartilage of mice that had undergone destabilization of the medial meniscus (DMM) surgery significantly reduced the cartilage destruction in this model, whereas introduction of SHMT-2 or MECP-2 increased the severity of cartilage destruction. Together, these results show that miR-370 and miR-373 contribute to the pathogenesis of OA and act as negative regulators of SHMT-2 and MECP-2, respectively.

MicroRNA-9 regulates survival of chondroblasts and cartilage integrity by targeting protogenin

BackgroundStudies have shown the roles of miR-9 and its validated target, protogenin (PRTG) in the differentiation of chondroblasts to chondrocyte and in the pathogenesis of osteoarthritis (OA). We hypothesized that miR-9 plays a distinct role in endochondral ossification and OA pathogenesis and the present study was undertaken to identify this role. In the studies, chondroblasts were isolated from limb bud of chick and mouse embryos and articular chondrocytes were isolated from rabbit and human cartilage. Osteoarthritic chondrocytes were isolated from cartilage from patients undergoing total knee replacement. Using these cells, we analyzed the changes in the expression of genes and proteins, tested the expression level of miR-9, and applied a target validation system. We also performed functional study of miR-9 and PRTG.ResultsWith the progression of chondrogenesis, decreased miR-9 level was observed at the time of numerous apoptotic cell deaths. And chondrocytes isolated from normal human articular cartilage expressed miR-9, and this expression was significantly reduced in OA chondrocytes, especially decreased its expression in parallel with the degree of cartilage degradation. Over-expression of PRTG induced the activation of caspase-3 signaling and increased apoptosis. However, the co-treatment with the miR-9 precursor or PRTG-specific siRNA blocked this apoptotic signaling.ConclusionThis study shows that PRTG is regulated by miR-9, plays an inhibitory action on survival of chondroblasts and articular chondrocytes during chondrogenesis and OA pathogenesis.

Coenzyme Q10 Ameliorates Pain and Cartilage Degradation in a Rat Model of Osteoarthritis by Regulating Nitric Oxide and Inflammatory Cytokines

ObjectiveTo investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).Materials and MethodsOA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.ResultsTreatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.ConclusionCoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.

Expression of MMP-1 in cartilage and synovium of experimentally induced rabbit ACLT traumatic osteoarthritis: immunohistochemical study

To observe the level and the distribution of MMP-1 in cartilage and synovium over the progression of OA in rabbit ACLT model, and to explore the relationship between the amount of MMP-1 expression and the degree of OA cartilage degradation. OA was induced in 20 rabbits by anterior cruciate ligament transection (ACLT) and ten rabbits were killed at 4 and 8 weeks after the operation, respectively. A further ten rabbits received unilateral knee arthrotomy as controls. Cartilage degradation was observed under dissecting microscope, immunohistochemical, and morphometric analysis were adopted to record the tissue level and distribution of MMP-1 in cartilage and synovium. Cartilage degradation in both ACLT groups was more severe than that in control group, and the degradation in 8-week ACLT group was more severe than that in 4-week ACLT group. MMP-1 was expressed predominantly in the superficial and upper intermediate layers of cartilage and in the lining layer of synovium. Its expression was increased steadily over the progression of OA both in cartilage and in synovium, but there was a little difference in the increase pattern between them: increase of MMP-1 in synovium lagged behind that in cartilage in early stage of OA. MMP-1 was involved in OA development in rabbit ACLT model and the amount of its expression was related with the degree of cartilage degradation. The increase of MMP-1 expression in synovium lagged behind that in cartilage, suggesting OA pathology was originated from cartilage, but synovitis may also paticipate in cartilage degradation, especially in middle and late stage of OA.

Chondrocyte death by apoptosis is associated with cartilage matrix degradation

To investigate the frequency of chondrocyte apoptosis in equine articular cartilage (AC) specimens and to examine the relationship between the process of cell death and the degree of cartilage degradation using a direct quantification of numbers of apoptotic cells and expression of active caspase-3. AC from equine metacarpophalangeal (MCP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints was used and each joint was graded macroscopically for cartilage degradation (macroscopic osteoarthritis (OA) score). Cartilage sections were graded using a 'modified' Mankin scoring system. Apoptosis of chondrocytes in cartilage sections was assessed morphologically by appearance of apoptotic features (direct method) and by expression of active caspase-3 using indirect immunohistochemistry. The extent of apoptosis assessed by the direct method did not show any relationship with increasing severity of OA (P=0.72). However, there was a significant positive correlation between 'modified' Mankin score and apoptosis determined by caspase-3, with the extent of apoptosis found to increase linearly with increasing severity of OA (r=0.44, P=0.0043). Caspase-3 expression was found to be significantly higher in the superficial and middle zones than in the deep zone (P<0.001). In the superficial, middle and deep zones, expression of caspase-3 was significantly higher in the MCP joint than in the PIP joint (P=0.013, P=0.0018 and P=0.029, respectively). Within the MCP joints, apoptosis was higher in the lateral compartment compared to the medial (P=0.053). The data presented in this study demonstrate that chondrocyte apoptosis is positively associated with degree of cartilage matrix damage and that the extent of apoptosis varies with cartilage zones and mechanical loading environment of the joint.

A correlation between knee cartilage degradation observed by arthroscopy and synovial proteinases activities

Objective A novel study has been carried out to characterize the amount and activity levels of metalloproteinases (i.e., MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13) and of their inhibitors (i.e., TIMP-1 and TIMP-2) in synovial fluid from patients ( n = 56) with different degrees of either chondral lesions or knee arthritis identified and classified by arthroscopy. Design and methods Zymographies, Western blotting and ELISA tests have been used to correlate the disease stage, as determined by arthroscopy, and both the amount and the activation state of different MMPs and of their inhibitors. Results Analysis of data obtained demonstrates that the degree of cartilage degradation, as seen by arthroscopy, is strictly related to the activity of some synovial MMPs, in particular MMP-2 and MMP-13 and on reduced inhibitory effect of MMP-2 by TIMP-2; in addition, a serine protease weighing about 125 kDa appears only in patients with severe cartilage degradation, i.e., with knee arthritis. Conclusions On the whole, this is the first study in which an analysis of synovial MMPs/other proteinases activity and TIMPs has been strictly related to arthroscopy results in patients with different degrees of osteoarthritis. Results indicate that an imbalance between specific MMP activities and the amount of TIMPs and of its inhibitory efficiency is crucial for the disease evolution and it is related to the disease stage.

New potential markers for cartilage degradation of the knee joint

To determine the correlation of biochemical markers with the degree of cartilage degradation. In a cross-sectional study, synovial fluid samples were obtained from 65 patients with cartilage lesions of the knee joint. The measured biochemical markers included MMP-1, MMP-3, and MMP-13, the tissue inhibitor of MMPs (TIMP-1), COMP, YKL-40, and tenascin. The marker levels were compared with the Outerbridge and the Noyes classification. For the majority of markers, the correlation coefficient was below r = 0.3. The highest correlation coefficients were obtained from tenascin (r = 0.66 and 0.67) and MMP-13 (r = 0.44 and 0.41). The overall results indicate that the majority of the tested markers is unspecific with regard to the different stages of the two classifications. However, tenascin and MMP-13 could be of clinical importance to indicate advanced stages. Yet the values of these markers in longitudinal studies are not known.

New potential markers for cartilage degradation of the knee joint

Objective: To determine the correlation of biochemical markers with the degree of cartilage degradation. Methods: In a cross-sectional study, synovial fluid samples were obtained from 65 patients with cartilage lesions of the knee joint. The measured biochemical markers included MMP-1, MMP-3, and MMP-13, the tissue inhibitor of MMPs (TIMP-1), COMP, YKL-40, and tenascin. The marker levels were compared with the Outerbridge and the Noyes classification. Results: For the majority of markers, the correlation coefficient was below r = 0.3. The highest correlation coefficients were obtained from tenascin (r = 0.66 and 0.67) and MMP-13 (r = 0.44 and 0.41). Conclusion: The overall results indicate that the majority of the tested markers is unspecific with regard to the different stages of the two classifications. However, tenascin and MMP-13 could be of clinical importance to indicate advanced stages. Yet the values of these markers in longitudinal studies are not known.