title: Relationship of age and body mass index to the expression of obesity and osteoarthritis-related genes in human meniscus.
abstract: OBJECTIVE
  Aging and obesity contribute to the initiation and progression of osteoarthritis with little information on their relation to gene expression in joint tissues, particularly the meniscus. Here, we test the hypothesis that patient age and body mass index (BMI) correlate with the expression of osteoarthritis- and obesity-related gene signatures in the meniscus.
  
  
  METHODS
  Meniscus was obtained from patients (N=68) undergoing arthroscopic partial meniscectomy. The mRNA expression of 24 osteoarthritis-related and 4 obesity-related genes in meniscus was assessed by quantitative real-time PCR. The relationship between gene expression and patient age and BMI was analyzed using Spearman's rank-order correlation. Hierarchical cluster dendrogram and heat map were generated to study inter-gene associations.
  
  
  RESULTS
  Age was negatively correlated (P<0.05) with the expression of MMP-1 (r=-0.447), NFκB2 (r=-0.361), NFκBIA (r=-0.312), IκBA (r=-0.308), IL-8 (r=-0.305), ADAMTS-4 (r=-0.294), APLN (apelin) (r=-0.250) and IL-6 (r=-0.244). Similarly, BMI was negatively correlated with the expression of APLN (r=-0.328), ACAN (r=-0.268) and MMP-1 (r=-0.261). After adjusting for the correlation between age and BMI (r=0.310; P=0.008), the only independent effect of BMI on gene expression was for APLN (r=-0.272). However, age had an independent effect on the expression on ADAMTS-4 (r=-0.253), MMP-1 (r=-0.399), IL-8 (r=-0.327), COL1A1 (r=-0.287), NFκBIA (r=-0.278), NFκB2 (r=-0.312) and IκBA (r=-0.299). The gene correlation analysis identified four clusters of potentially relevant genes: transcription factors, matrix-degrading enzymes, cytokines and chemokines, and obesity genes.
  
  
  CONCLUSIONS
  Age and BMI were negatively correlated with several osteoarthritis- and obesity-related genes. Although the bulk of these changes appeared to be driven by age, expression of APLN was related to BMI. Inter-gene correlation analysis implicated a common role for strongly correlated genes. Although age-related variations in gene expression appear to be more relevant than obesity-related differences for the role of the meniscus in osteoarthritis development, further investigation into the role of APLN in meniscus and joint health is warranted.
authors: Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St Louis, MO, USA.
authors: M F
authors: MF
authors: Rai
authors: L J
authors: LJ
authors: Sandell
authors: J M
authors: JM
authors: Cheverud
authors: R H
authors: RH
authors: Brophy
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000073861:Apelin; D015992:Body Mass Index; D002358:Cartilage, Articular / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008592:Menisci, Tibial / Q000378:metabolism*; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D009765:Obesity / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D040081:Protein Array Analysis; D060888:Real-Time Polymerase Chain Reaction; D000070600:Tibial Meniscus Injuries; D014481:United States / Q000453:epidemiology
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D020672:I-kappa B Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D020781:Matrix Metalloproteinase 1; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human