title: Molecular analysis of age and sex-related gene expression in meniscal tears with and without a concomitant anterior cruciate ligament tear.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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]-1α, IL-1β, IL-6, and tumor necrosis factor-alpha [TNFα]), 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 (NFκB2 [nuclear factor kappa B2], NFκBIA [NF-kappa B inhibitor alpha], and IκBA [inhibitor of kappa B alpha]), and matrix components (bone morphogenetic protein [BMP]-2, type-I collagen alpha 1 [Col1a1], Col2a1, and aggrecan).
  
  
  RESULTS
  Expression of IL-1β (p = 0.02), ADAMTS-5 (p = 0.001), MMP-1 (p = 0.007), MMP-9 (p = 0.002), MMP-13 (p = 0.01), and NFκB2 (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-1β (p = 0.01), TNFα (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 &lt; 0.05) of all ages with combined injuries.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine, 14532 South Outer Forty Drive, Chesterfield, MO 63017, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brophy
authors.forename: Muhammad Farooq
authors.initials: MF
authors.lastname: Rai
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Adelina
authors.initials: A
authors.lastname: Torgomyan
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Sandell
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D053674:Aggrecans / Q000235:genetics; D000070598:Anterior Cruciate Ligament Injuries; D054405:Chemokine CCL3 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D007718:Knee Injuries / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D011348:Procollagen N-Endopeptidase / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors; D000070600:Tibial Meniscus Injuries; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D053674:Aggrecans; D054405:Chemokine CCL3; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D053509:Matrix Metalloproteinase 13; D011348:Procollagen N-Endopeptidase; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human