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Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear.

ABSTRACT: The meniscus plays critical roles in the knee, contributing to load transmission, shock absorption, and joint stability. Little is known about gene expression in meniscal tears, particularly in relation to injury pattern and patient age and sex. The purpose of this study was to test the hypothesis that gene expression in meniscal tears varies depending on patient age and sex and whether the anterior cruciate ligament (ACL) is also torn.Meniscal tissue from twenty-eight patients with an isolated meniscal tear or a meniscal tear with a concomitant ACL tear was collected at the time of clinically indicated partial meniscectomy. Messenger RNA (mRNA) expression was examined by quantitative real-time polymerase chain reaction for molecular markers of osteoarthritis including proinflammatory cytokines (interleukin [IL]-1?, IL-1?, IL-6, and tumor necrosis factor-alpha [TNF?]), chemokines (IL-8, CCL3, CCL3L1, CXCL1, CXCL3, CXCL6, and CCL20), aggrecanases (ADAMTS-4 [a disintegrin and metalloproteinase with thrombospondin type-4 motifs] and ADAMTS-5), matrix metalloproteinases (MMP-1, MMP-3, MMP-9, and MMP-13), transcription factors (NF?B2 [nuclear factor kappa B2], NF?BIA [NF-kappa B inhibitor alpha], and I?BA [inhibitor of kappa B alpha]), and matrix components (bone morphogenetic protein [BMP]-2, type-I collagen alpha 1 [Col1a1], Col2a1, and aggrecan).Expression of IL-1? (p = 0.02), ADAMTS-5 (p = 0.001), MMP-1 (p = 0.007), MMP-9 (p = 0.002), MMP-13 (p = 0.01), and NF?B2 (p = 0.01) was significantly higher in patients with a meniscal tear who were under the age of forty years than it was in those over the age of forty years. Similarly, the expression of ADAMTS-4 (p = 0.002), ADAMTS-5 (p = 0.02), MMP-1 (p = 0.02), and MMP-13 (p = 0.0002) was higher in patients with a meniscal tear and an ACL tear who were under the age of forty years than it was in those over forty years. In patients with a meniscal tear and an ACL tear, the expression of IL-1? (p = 0.01), TNF? (p = 0.02), MMP-13 (p = 0.004), CCL3 (p = 0.03), and CCL3L1 (p = 0.03) was significantly higher, while that of aggrecan (p = 0.03) was lower, than that in patients with a meniscal tear alone. The only sex-based difference in gene expression was higher levels of CCL3L1 in female patients (p < 0.05) of all ages with combined injuries.These findings suggest clinically relevant differences in the response of the knee to meniscal tears on the basis of patient age and sex. Elevated expression levels of arthritis-related markers indicate an increased catabolic response in patients under forty years old. Higher expression of catabolic markers in patients with meniscal and ACL tears suggests this combined injury pattern is more likely to lead to the development of osteoarthritis. Catabolic activity in meniscal tissue may predict patients who are at risk for progression of osteoarthritis following partial meniscectomy.

SUBMITTER: Brophy RH

PROVIDER: S-EPMC3284860 | biostudies-other | 2012 Mar

REPOSITORIES: biostudies-other

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Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear.

Brophy Robert H RH Rai Muhammad Farooq MF Zhang Zhiqi Z Torgomyan Adelina A Sandell Linda J LJ

The Journal of bone and joint surgery. American volume 20120301 5

<h4>Background</h4>The meniscus plays critical roles in the knee, contributing to load transmission, shock absorption, and joint stability. Little is known about gene expression in meniscal tears, particularly in relation to injury pattern and patient age and sex. The purpose of this study was to test the hypothesis that gene expression in meniscal tears varies depending on patient age and sex and whether the anterior cruciate ligament (ACL) is also torn.<h4>Methods</h4>Meniscal tissue from twen ...[more]

PMID: 22362494

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Project description:BackgroundWhen meniscal repair is performed during anterior cruciate ligament (ACL) reconstruction (ACLR), the effect of ACL graft type on meniscal repair outcomes is unclear.HypothesisThe authors hypothesized that meniscal repairs would fail at the lowest rate when concomitant ACLR was performed with bone--patellar tendon--bone (BTB) autograft.Study designCohort study; Level of evidence, 3.MethodsPatients who underwent meniscal repair at primary ACLR were identified from a longitudinal, prospective cohort. Meniscal repair failures, defined as any subsequent surgical procedure addressing the meniscus, were identified. A logistic regression model was built to assess the association of graft type, patient-specific factors, baseline Marx activity rating score, and meniscal repair location (medial or lateral) with repair failure at 6-year follow-up.ResultsA total of 646 patients were included. Grafts used included BTB autograft (55.7%), soft tissue autograft (33.9%), and various allografts (10.4%). We identified 101 patients (15.6%) with a documented meniscal repair failure. Failure occurred in 74 of 420 (17.6%) isolated medial meniscal repairs, 15 of 187 (8%) isolated lateral meniscal repairs, and 12 of 39 (30.7%) of combined medial and lateral meniscal repairs. Meniscal repair failure occurred in 13.9% of patients with BTB autografts, 17.4% of patients with soft tissue autografts, and 19.4% of patients with allografts. The odds of failure within 6 years of index surgery were increased more than 2-fold with allograft versus BTB autograft (odds ratio = 2.34 [95% confidence interval, 1.12-4.92]; P = .02). There was a trend toward increased meniscal repair failures with soft tissue versus BTB autografts (odds ratio = 1.41 [95% confidence interval, 0.87-2.30]; P = .17). The odds of failure were 68% higher with medial versus lateral repairs (P < .001). There was a significant relationship between baseline Marx activity level and the risk of subsequent meniscal repair failure; patients with either very low (0-1 points) or very high (15-16 points) baseline activity levels were at the highest risk (P = .004).ConclusionMeniscal repair location (medial vs lateral) and baseline activity level were the main drivers of meniscal repair outcomes. Graft type was ranked third, demonstrating that meniscal repairs performed with allograft were 2.3 times more likely to fail compared with BTB autograft. There was no significant difference in failure rates between BTB versus soft tissue autografts.RegistrationNCT00463099 (ClinicalTrials.gov identifier).

Project description:PurposeTo evaluate the incidence of complete lateral meniscal posterior root tears (LMPRTs) repaired at revision as compared with primary anterior cruciate ligament (ACL) reconstruction (PACLR) and to determine whether other demographic or surgical characteristics were associated with LMPRTs needing repair.MethodsA chart review was performed to identify the PACLR and revision ACL reconstruction (RACLR) cohorts. Demographic and surgical characteristics were recorded. Cases with concurrent lateral meniscal posterior root repair were identified. Cases were classified as acute (<5 months) or chronic (>5 months) based on the time from reported injury to surgery. Tunnel malposition in revision cases was recorded if either tunnel or both tunnels were malpositioned on radiographs and magnetic resonance imaging.ResultsData from 167 cases, 140 PACLR and 27 RACLR cases, were included. The cohorts had similar demographic characteristics including age, sex, and lateral meniscal injury. The overall incidence of lateral meniscal root repair in ACL reconstruction patients was 12.6% (21 of 167 patients). The incidence of LMPRT repair was 7.1% (10 of 140 patients) in the PACLR cohort versus 40.7% (11 of 27 patients) in the RACLR cohort. The revision cohort was significantly more likely to have a chronic injury (66.7% [18 of 27 patients] vs 31.4% [44 of 140 patients]). The most significant predictor of concurrent lateral meniscal posterior root repair was RACLR versus PACLR for both univariate and multivariate logistic regression analyses (χ2 = 20.603; P < .0001; odds ratio, 13.887; 95% confidence interval, 1.531-125.993). Analysis of tunnel positions for the revision group revealed that PACLR tunnel malposition was a significant predictor of LMPRTs (χ2 = 4.91, P = .027).ConclusionsComplete LMPRTs warranting repair are encountered with a significantly greater frequency at RACLR as compared with PACLR. The overall incidence of LMPRT repair at RACLR is high. In this cohort, LMPRT repair in RACLR cases was associated with tunnel malposition of the PACLR.Level of evidenceLevel III, retrospective cohort study.

Project description:BackgroundAn anterior cruciate ligament (ACL) tear is a common knee injury, particularly among young and active individuals. Little is known, however, about the societal impacts of ACL tears, which could be large given the typical patient age and increased lifetime risk of knee osteoarthritis. This study evaluates the cost-effectiveness of ACL reconstruction compared with structured rehabilitation only.MethodsA cost-utility analysis of ACL reconstruction compared with structured rehabilitation only was conducted with use of a Markov decision model over two time horizons: the short to intermediate term (six years), on the basis of Level-I evidence derived from the KANON Study and the Multicenter Orthopaedic Outcomes Network (MOON) database; and the lifetime, on the basis of a comprehensive literature review. Utilities were assessed with use of the SF-6D. Costs (in 2012 U.S. dollars) were estimated from the societal perspective and included the effects of the ACL tear on work status, earnings, and disability. Effectiveness was expressed as quality-adjusted life years (QALYs) gained.ResultsIn the short to intermediate term, ACL reconstruction was both less costly (a cost reduction of $4503) and more effective (a QALY gain of 0.18) compared with rehabilitation. In the long term, the mean lifetime cost to society for a typical patient undergoing ACL reconstruction was $38,121 compared with $88,538 for rehabilitation. ACL reconstruction resulted in a mean incremental cost savings of $50,417 while providing an incremental QALY gain of 0.72 compared with rehabilitation. Effectiveness gains were driven by the higher probability of an unstable knee and associated lower utility in the rehabilitation group. Results were most sensitive to the rate of knee instability after initial rehabilitation.ConclusionsACL reconstruction is the preferred cost-effective treatment strategy for ACL tears and yields reduced societal costs relative to rehabilitation once indirect cost factors, such as work status and earnings, are considered. The cost of an ACL tear over the lifetime of a patient is substantial, and resources should be directed to developing innovations for injury prevention and for altering the natural history of an ACL injury.

Dataset Information

Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear.

Publications

Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear.

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