Transcriptional analysis of micro-dissected articular cartilage in post-traumatic murine osteoarthritis.
Osteoarthritis Cartilage
; 23(4): 616-28, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25545425
ABSTRACT
OBJECTIVE:
Identify gene changes in articular cartilage of the medial tibial plateau (MTP) at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice. Compare our data with previously published datasets to ascertain dysregulated pathways and genes in osteoarthritis (OA).DESIGN:
RNA was extracted from the ipsilateral and contralateral MTP cartilage, amplified, labelled and hybridized on Illumina WGv2 microarrays. Results were confirmed by real-time polymerase chain reaction (PCR) for selected genes.RESULTS:
Transcriptional analysis and network reconstruction revealed changes in extracellular matrix and cytoskeletal genes induced by DMM. TGFß signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (Fn1) is a hub in a reconstructed network at 2 weeks. Regulated genes decrease over time. By 8 weeks fibromodulin (Fmod) and tenascin N (Tnn) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets identified genes overlapping between our array and eight other studies.CONCLUSIONS:
Cartilage contributes a minute percentage to the RNA extracted from the whole joint (<0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time dissipating by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFß. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify may warrant further investigation as biomarkers or modulators of OA.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Wounds and Injuries
/
Menisci, Tibial
/
Signal Transduction
/
Cartilage, Articular
/
Osteoarthritis, Knee
/
Microarray Analysis
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Osteoarthritis Cartilage
Journal subject:
ORTOPEDIA
/
REUMATOLOGIA
Year:
2015
Type:
Article