Journal Article

RNA Microarray Analysis of Macroscopically Normal Articular Cartilage from Knees Undergoing Partial Medial Meniscectomy: Potential Prediction of the Risk for Developing Osteoarthritis

Brophy, Robert H., Sandell, Linda J., Wright, Rick W., Rai, Muhammad Farooq, Zhang, Bo

2016

Overview

(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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Age / Age Factors / Aged / Aging / Alleles / Arthritis / Biocompatibility / Biological activity / Biological computing / Biology / Biology and Life Sciences / Body mass / Body Mass Index / Calcification / Cartilage / Cartilage (articular) / Cartilage diseases / Cartilage, Articular - pathology / Clusters / Complications and side effects / Cytokines / Degeneration / DNA microarrays / Female / Femur / Gene expression / Gene Expression Profiling / Gene Expression Regulation / Genetic aspects / Genetic screening / Genome-Wide Association Study / Genomes / Humans / Inflammation / Joint surgery / Knee / Knee Joint - pathology / Knee surgery / Magnetic resonance / Male / Medicine / Medicine and Health Sciences / Menisci, Tibial - pathology / Menisci, Tibial - surgery / Meniscus / Microarray Analysis / Microfluidics / Middle Aged / Obesity / Osteoarthritis / Osteoarthritis, Knee - genetics / Osteoarthritis, Knee - pathology / Patients / Polymerase Chain Reaction / Predictions / Reproducibility of Results / Research and Analysis Methods / Ribonucleic acid / Risk / Risk Factors / RNA / RNA, Messenger - genetics / RNA, Messenger - metabolism / Sex / Studies / Surgery / Tearing / Transcriptome - genetics / Tumor necrosis factor-TNF