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Distinct degenerative phenotype of articular cartilage from knees with meniscus tear compared to knees with osteoarthritis.

ABSTRACT: OBJECTIVE:To compare the transcriptome of articular cartilage from knees with meniscus tears to knees with end-stage osteoarthritis (OA). DESIGN:Articular cartilage was collected from the non-weight bearing medial intercondylar notch of knees undergoing arthroscopic partial meniscectomy (APM; N = 10, 49.7 ± 10.8 years, 50% females) for isolated medial meniscus tears and knees undergoing total knee arthroplasty (TKA; N = 10, 66.0 ± 7.6 years, 70% females) due to end-stage OA. Ribonucleic acid (RNA) preparation was subjected to SurePrint G3 human 8 × 60K RNA microarrays to probe differentially expressed transcripts followed by computational exploration of underlying biological processes. Real-time polymerase chain reaction amplification was performed on selected transcripts to validate microarray data. RESULTS:We observed that 81 transcripts were significantly differentially expressed (45 elevated, 36 repressed) between APM and TKA samples (? 2 fold) at a false discovery rate of ? 0.05. Among these, CFD, CSN1S1, TSPAN11, CSF1R and CD14 were elevated in the TKA group, while CHI3L2, HILPDA, COL3A1, COL27A1 and FGF2 were highly expressed in APM group. A few long intergenic non-coding RNAs (lincRNAs), small nuclear RNAs (snoRNAs) and antisense RNAs were also differentially expressed between the two groups. Transcripts up-regulated in TKA cartilage were enriched for protein localization and activation, chemical stimulus, immune response, and toll-like receptor signaling pathway. Transcripts up-regulated in APM cartilage were enriched for mesenchymal cell apoptosis, epithelial morphogenesis, canonical glycolysis, extracellular matrix organization, cartilage development, and glucose catabolic process. CONCLUSIONS:This study suggests that APM and TKA cartilage express distinct sets of OA transcripts. The gene profile in cartilage from TKA knees represents an end-stage OA whereas in APM knees it is clearly earlier in the degenerative process.

SUBMITTER: Rai MF

PROVIDER: S-EPMC6536326 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Distinct degenerative phenotype of articular cartilage from knees with meniscus tear compared to knees with osteoarthritis.

Rai M F MF Tycksen E D ED Cai L L Yu J J Wright R W RW Brophy R H RH

Osteoarthritis and cartilage 20190221 6

<h4>Objective</h4>To compare the transcriptome of articular cartilage from knees with meniscus tears to knees with end-stage osteoarthritis (OA).<h4>Design</h4>Articular cartilage was collected from the non-weight bearing medial intercondylar notch of knees undergoing arthroscopic partial meniscectomy (APM; N = 10, 49.7 ± 10.8 years, 50% females) for isolated medial meniscus tears and knees undergoing total knee arthroplasty (TKA; N = 10, 66.0 ± 7.6 years, 70% females) due to end-stage OA. Ribon ...[more]

PMID: 30797944

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Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.

Project description:OBJECTIVES:To assess the long-term effects of arthroscopic partial meniscectomy (APM) on the development of radiographic knee osteoarthritis, and on knee symptoms and function, at 5 years follow-up. DESIGN:Multicentre, randomised, participant- and outcome assessor-blinded, placebo-surgery controlled trial. SETTING:Orthopaedic departments in five public hospitals in Finland. PARTICIPANTS:146 adults, mean age 52 years (range 35-65 years), with knee symptoms consistent with degenerative medial meniscus tear verified by MRI scan and arthroscopically, and no clinical signs of knee osteoarthritis were randomised. INTERVENTIONS:APM or placebo surgery (diagnostic knee arthroscopy). MAIN OUTCOME MEASURES:We used two indices of radiographic knee osteoarthritis (increase in Kellgren and Lawrence grade ?1, and increase in Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing and osteophyte sum score, respectively), and three validated patient-relevant measures of knee symptoms and function (Western Ontario Meniscal Evaluation Tool (WOMET), Lysholm, and knee pain after exercise using a numerical rating scale). RESULTS:There was a consistent, slightly greater risk for progression of radiographic knee osteoarthritis in the APM group as compared with the placebo surgery group (adjusted absolute risk difference in increase in Kellgren-Lawrence grade ?1 of 13%, 95% CI -2% to 28%; adjusted absolute mean difference in OARSI sum score 0.7, 95% CI 0.1 to 1.3). There were no relevant between-group differences in the three patient-reported outcomes: adjusted absolute mean differences (APM vs placebo surgery), -1.7 (95% CI -7.7 to 4.3) in WOMET, -2.1 (95% CI -6.8 to 2.6) in Lysholm knee score, and -0.04 (95% CI -0.81 to 0.72) in knee pain after exercise, respectively. The corresponding adjusted absolute risk difference in the presence of mechanical symptoms was 18% (95% CI 5% to 31%); there were more symptoms reported in the APM group. All other secondary outcomes comparisons were similar. CONCLUSIONS:APM was associated with a slightly increased risk of developing radiographic knee osteoarthritis and no concomitant benefit in patient-relevant outcomes, at 5 years after surgery. TRIAL REGISTRATION:ClinicalTrials.gov (NCT01052233 and NCT00549172).

Project description:Objectives(i) To provide baseline knowledge of gene expression in macroscopically normal articular cartilage, (ii) to test the hypothesis that age, body-mass-index (BMI), and sex are associated with cartilage RNA transcriptome, and (iii) to predict individuals at potential risk for developing "pre-osteoarthritis" (OA) based on screening of genetic risk-alleles associated with OA and gene transcripts differentially expressed between normal and OA cartilage.DesignHealthy-appearing cartilage was obtained from the medial femoral notch of 12 knees with a meniscus tear undergoing arthroscopic partial meniscectomy. Cartilage had no radiographic, magnetic-resonance-imaging or arthroscopic evidence for degeneration. RNA was subjected to Affymetrix microarrays followed by validation of selected transcripts by microfluidic digital polymerase-chain-reaction. The underlying biological processes were explored computationally. Transcriptome-wide gene expression was probed for association with known OA genetic risk-alleles assembled from published literature and for comparison with gene transcripts differentially expressed between healthy and OA cartilage from other studies.ResultsWe generated a list of 27,641 gene transcripts in healthy cartilage. Several gene transcripts representing numerous biological processes were correlated with age and BMI and differentially expressed by sex. Based on disease-specific Ingenuity Pathways Analysis, gene transcripts associated with aging were enriched for bone/cartilage disease while the gene expression profile associated with BMI was enriched for growth-plate calcification and OA. When segregated by genetic risk-alleles, two clusters of study patients emerged, one cluster containing transcripts predicted by risk studies. When segregated by OA-associated gene transcripts, three clusters of study patients emerged, one of which is remarkably similar to gene expression pattern in OA.ConclusionsOur study provides a list of gene transcripts in healthy-appearing cartilage. Preliminary analysis into groupings based on OA risk-alleles and OA-associated gene transcripts reveals a subset of patients expressing OA transcripts. Prospective studies in larger cohorts are needed to assess whether these patterns are predictive for OA.

Dataset Information

Distinct degenerative phenotype of articular cartilage from knees with meniscus tear compared to knees with osteoarthritis.

Publications

Distinct degenerative phenotype of articular cartilage from knees with meniscus tear compared to knees with osteoarthritis.

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