Genome-wide expression profiles of subchondral bone in osteoarthritis.
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INTRODUCTION: The aim of this study was to evaluate, for the first time, the differences in gene expression profiles of normal and osteoarthritic (OA) subchondral bone in human subjects. METHODS: Following histological assessment of the integrity of overlying cartilage and the severity of bone abnormality by micro-computed tomography, we isolated total RNA from regions of interest from human OA (n = 20) and non-OA (n = 5) knee lateral tibial (LT) and medial tibial (MT) plateaus. A whole-genome profiling study was performed on an Agilent microarray platform and analyzed using Agilent GeneSpring GX11.5. Confirmatory quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was performed on samples from 9 OA individuals to confirm differential expression of 85 genes identified by microarray. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples. RESULTS: A total of 972 differentially expressed genes were identified (fold change ≥ ± 2, P ≤0.05) between LT (minimal degeneration) and MT (significant degeneration) regions from OA samples; these data implicated 279 canonical pathways in IPA. The qRT-PCR data strongly confirmed the accuracy of microarray results (R2 = 0.58, P <0.0001). Novel pathways were identified in this study including Periostin (POSTN) and Leptin (LEP), which are implicated in bone remodeling by osteoblasts. CONCLUSIONS: To the best of our knowledge, this study represents the most comprehensive direct assessment to date of gene expression profiling in OA subchondral bone. This study provides insights that could contribute to the development of new biomarkers and therapeutic strategies for OA.
Bone and Bones
Gene Expression Profiling
Reverse Transcriptase Polymerase Chain Reaction
Published Version (Please cite this version)10.1186/ar4380
Publication InfoChou, Ching-Heng; Wu, Chia-Chun; Song, I-Wen; Chuang, Hui-Ping; Lu, Liang-Suei; Chang, Jen-Huei; ... Lee, Ming Ta Michael (2013). Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthritis Res Ther, 15(6). pp. R190. 10.1186/ar4380. Retrieved from https://hdl.handle.net/10161/10868.
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Professor Emeritus of Pediatrics
Our overall research interests are in translational research. We aim at translating the promise of genomic medicine into clinical reality. Specific projects at present time include: 1). Identification of novel genes/targets associated with human diseases. This includes susceptibility genes for common multi-factorial diseases and adverse drug reactions. Genetic epidemiology, mouse ENU mutagenesis, bioinformatics and proteomics are some approaches that we use in identif
Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis. Osteoarthritis is the most common form of joint disease in man and its incidence increases with age. It is a problem of increasing concern to the medical community due to the increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist, I endeavor to study this disease from bedside to bench. The work in this laboratory focuses on osteoarthritis and deals w
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