Genome-wide expression profiles of subchondral bone in osteoarthritis.

Chou, Ching-Heng

Wu, Chia-Chun

Song, I-Wen

Chuang, Hui-Ping

Lu, Liang-Suei

Chang, Jen-Huei

Kuo, San-Yuan

Lee, Chian-Her

Wu, Jer-Yuarn

Chen, Yuan-Tsong

Kraus, Virginia Byers

Lee, Ming Ta Michael

England

2015-11-10T22:33:37Z

2013

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.

http://www.ncbi.nlm.nih.gov/pubmed/24229462

ar4380

1478-6362

https://hdl.handle.net/10161/10868

eng

Springer Science and Business Media LLC

Arthritis Res Ther

10.1186/ar4380

Aged

Bone and Bones

Female

Gene Expression Profiling

Humans

Immunohistochemistry

Male

Middle Aged

Osteoarthritis, Knee

Reverse Transcriptase Polymerase Chain Reaction

Transcriptome

Genome-wide expression profiles of subchondral bone in osteoarthritis.

Journal article

Kraus, Virginia Byers|0000-0001-8173-8258

http://www.ncbi.nlm.nih.gov/pubmed/24229462

R190

6

Clinical Science Departments

Duke

Duke Molecular Physiology Institute

Institutes and Centers

Medicine

Medicine, Rheumatology and Immunology

Orthopaedics

Pathology

Pediatrics

Pediatrics, Medical Genetics

School of Medicine

Published

15