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Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

ABSTRACT: Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover.ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes were quantified in the articular cartilage, synovium, injured ligament, and the provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS 846) were quantified in the serum and synovial fluid. Histologic assessment of the cartilage integrity (OARSI scoring) was also performed.MMP-1 gene expression was upregulated in the articular cartilage, synovium and ligament after ACL injury. MMP-13 expression was suppressed in the articular cartilage, but upregulated 100-fold in the synovium and ligament. ADAMTS-4 was upregulated in the synovium and ligament but not in the articular cartilage. The concentration of collagen degradation fragments (C2C) in the synovial joint fluid nearly doubled in the first five days after injury.We conclude that upregulation of genes coding for proteins capable of degrading cartilage ECM is seen within the first few days after ACL injury, and this response is seen not only in chondrocytes, but also in cells in the synovium, ligament and provisional scaffold.

SUBMITTER: Haslauer CM

PROVIDER: S-EPMC3917322 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

Haslauer C M CM Elsaid K A KA Fleming B C BC Proffen B L BL Johnson V M VM Murray M M MM

Osteoarthritis and cartilage 20130913 12

<h4>Objective</h4>Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover.<h4>Methods</h4>ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 a ...[more]

PMID: 24036379

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Project description:BackgroundOsteoarthritis (OA) is a debilitating, progressive joint disease.MethodsSimilar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone.ResultsLocal regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery.ConclusionsIn summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease.

Project description:BackgroundIt is still controversial whether the combination of anterior cruciate ligament (ACL) reconstruction and extra-articular reconstruction (EAR) have good clinical efficacy. This meta-analysis aims systematically to compare the clinical effectiveness of ACL reconstruction and combined reconstruction.MethodsElectronic databases, including Medline/PubMed, Embase and the Cochrane Library, were systematically searched to identify targeted studies. A meta-analysis were performed to pool the outcome estimates of interest, such as the Lysholm, International Knee Documentation Committee (IKDC) and Tegner scores and the results from the KT-1000/2000 arthrometer test, the Lachman test and the pivot shift test.ResultsTwelve studies involving 1146 knees were identified. Compared with single ACL reconstruction, combined reconstruction had better results for a pivot shift of grade 1 (relative ratio [RR] = 0.88, 95% CI: 0.83-0.94) and grade 2 (RR = 0.95, 95% CI: 0.91-0.99) rather than grade 3 (RR = 0.98, 95% CI: 0.90-1.06) and no statistically significant difference for both Lachman grade 1 (RR = 0.96, 95% CI: 0.89-1.05) and grade 2 (RR = 0.96, 95% CI: 0.90-1.03). Combined reconstruction resulted in significant improvements on the instrumented joint laxity test when considering a failure standard of more than 5 mm (a side-to-side arthrometric difference) (RR = 0.94, 95% CI: 0.89-0.98) rather than 3 mm (RR = 0.94, 95% CI: 0.86-1.03). Moreover, combined reconstruction increased the IKDC score at the 12-month (weighted mean difference [WMD] = - 6.38, 95% CI: - 9.66 to - 3.10), 24-month (WMD = - 5.60, 95% CI: - 8.54 to - 2.66) and 36-month follow-ups (WMD = - 4.71, 95% CI: - 7.59 to - 1.83) and the Tegner score at the 36-month follow-up (WMD = - 0.53, 95% CI: - 0.97 to - 0.09), but it did not increase the Lysholm score at the 36-month follow-up (WMD = - 0.84, 95% CI: - 2.02 to 0.34).ConclusionWith the advances in reconstruction techniques, combined reconstructions were found to be effective in improving rotational stability and to lead to good functional scores. However, obviously, the combined reconstruction technique is more time-consuming and requires an additional incision, which is not suitable for all ACL-deficient patients. Therefore, programs should be personalized and customized for the specific situation of each patient.

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Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

Publications

Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

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