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Updated: Apr 19, 2026
Destabilization of the Medial Meniscus and Cartilage Scratch Murine Model of Accelerated Osteoarthritis
Published on: July 6, 2022
Transcriptional analysis of micro-dissected articular cartilage in post-traumatic murine osteoarthritis
M D Gardiner1, T L Vincent1, C Driscoll1
1Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK.
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. TGFβ 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 TGFβ. 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.
Insights
Gene expression changes in mouse knee cartilage after meniscus injury reveal early extracellular matrix alterations that decrease over time. Identified genes and pathways may serve as osteoarthritis biomarkers.
Area of Science:
- Molecular Biology
- Genomics
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown.
- Understanding early molecular changes in articular cartilage is crucial for developing effective OA treatments.
Purpose of the Study:
- To identify gene expression alterations in mouse medial tibial plateau (MTP) cartilage at 2, 4, and 8 weeks post-destabilization of the medial meniscus (DMM).
- To compare these findings with existing datasets to identify dysregulated pathways and genes relevant to OA.
- To explore potential biomarkers and therapeutic targets for OA.
Main Methods:
- RNA extraction from ipsilateral and contralateral MTP cartilage following DMM surgery in mice.
- Hybridization on Illumina WGv2 microarrays for transcriptional analysis.
- Validation of selected gene expression using real-time polymerase chain reaction (PCR).
- Bioinformatic network reconstruction and comparison with published OA gene sets.
Main Results:
- Destabilization of the medial meniscus (DMM) induced significant changes in extracellular matrix and cytoskeletal genes.
- Early (2 weeks) dysregulation of TGFβ signaling, complement, and coagulation cascade genes observed.
- Fibronectin (Fn1) identified as a key gene in early network changes.
- Gene expression alterations diminished over time, with only fibromodulin (Fmod) and tenascin N (Tnn) dysregulated by 8 weeks.
- Overlapping genes and pathways identified when compared to human and rodent OA datasets.
Conclusions:
- Articular cartilage, despite low RNA contribution, shows sensitive gene expression changes post-DMM.
- Transcriptional reprogramming in cartilage following DMM is transient, waning by 8 weeks.
- Common pathways (focal adhesion, actin cytoskeleton regulation, TGFβ) and genes (Jag1, Tspan2, Nbl1, Ndrg2) across studies suggest potential OA biomarkers or therapeutic targets.
