title: RNA Microarray Analysis of Macroscopically Normal Articular Cartilage from Knees Undergoing Partial Medial Meniscectomy: Potential Prediction of the Risk for Developing Osteoarthritis.
abstract: (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.
  
  
  
  Healthy-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.
  
  
  
  We 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.
  
  
  
  Our 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.
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, Missouri, United States of America.
authors.forename: Muhammad Farooq
authors.identifier: 0000-0003-4826-4331
authors.initials: MF
authors.lastname: Rai
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, Missouri, United States of America.|Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, Missouri, United States of America.|Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Sandell
authors.affiliation: Department of Developmental Biology, Center of Regenerative Medicine, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, Missouri, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, Missouri, United States of America.
authors.forename: Rick W
authors.initials: RW
authors.lastname: Wright
authors.affiliation: Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine at Barnes Jewish Hospital, St. Louis, Missouri, United States of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brophy
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D002358:Cartilage, Articular / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D007719:Knee Joint / Q000473:pathology*; D008297:Male; D008592:Menisci, Tibial / Q000473:pathology / Q000601:surgery*; D046228:Microarray Analysis; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012307:Risk Factors; D059467:Transcriptome / Q000235:genetics
chemical_list: D012333:RNA, Messenger