Genome-wide expression profiles of subchondral bone in osteoarthritis
1 Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Road, Nankang District, Taipei 11529, Taiwan
2 National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Road, Nankang District, Taipei 11529, Taiwan
3 Department of Pathology, Duke University School of Medicine, DUMC 3712, Durham, NC 27710, USA
4 Department of Orthopaedic Surgery, Tri-Service General Hospital, National Defense Medical Center, 325, Sec. 2, Cheng-gung Rd., Neihu Dist., Taipei 11472, Taiwan
5 Graduate Institute of Life Sciences, Tri-Service General Hospital, National Defense Medical Center, 114 No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei 114, Taiwan
6 Translational Resource Center for Genomic Medicine, Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Nankang District, Taipei 11529, Taiwan
7 Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
8 Department of Orthopedics, Taipei Medical University Hospital, 250 Wu-Hsing Street, Taipei 110, Taiwan
9 Department of Pediatrics, Duke University School of Medicine, DUMC 3352, Durham, NC 27710, USA
10 Department of Medicine, Duke University School of Medicine, 2301 Erwin Road, Room 1102, Durham, NC 27710, USA
11 Graduate Institute of Chinese Medical Science, China Medical University, No.91 Hsueh-Shih Road, Taichung 40402, Taiwan
12 Laboratory for International Alliance on Genomic Research, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Arthritis Research & Therapy 2013, 15:R190 doi:10.1186/ar4380Published: 15 November 2013
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.
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.
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.
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.