Table 1.
Examples of gene modulations in osteoarthritis (OA) models with discrepancies
| Human gene |
PMID | Intervention | Effect on protein product | OA model | Observed effect | Inferred gene effect | Specificity | Species |
| Mixed effects between models and tissue specificity | ||||||||
| EZH2 | 30327434 | Knockout | Removal | Spontaneous | No effect | No effect | Cartilage | Mouse |
| 31910305 | Knockout | Removal | Surgical − MM | Detrimental | Protective | Cartilage inducible | Mouse | |
| 27539752 | EPZ005687 | Inhibition | Surgical − ACLT | Protective | Detrimental | Articular cavity | Mouse | |
| Opposite effects between models | ||||||||
| MINK1 | 31647983 | Knockout | Removal | Spontaneous | Protective | Detrimental | Global | Mouse |
| Knockout | Removal | Surgical − DMM | Detrimental | Protective | Global | Mouse | ||
| Detrimental effects with any gene modulation | ||||||||
| TTR | 28941045 | Knockout | Removal | Surgical − DMM | Detrimental | Detrimental | Global | Mouse |
| Knockout | Removal | Spontaneous | Detrimental | Detrimental | Global | Mouse | ||
| Overexpression | Overexpression | Surgical − DMM | Detrimental | Protective | Global | Mouse | ||
| Effect observed in only one type of model | ||||||||
| CD9 | 27784871 | Knockout | Removal | Surgical - MML+ MCL | No effect | No effect | Global | Mouse |
| Knockout | Removal | Spontaneous | Protective | Detrimental | Global | Mouse | ||
| TLR4 | 31044181 | Knockout | Removal | High fat diet | Protective | Detrimental | Global | Mouse |
| 26245312 | Knockout | Removal | Surgical − DMM | No effect | No effect | Global | Mouse | |
| 24703622 | Knockout | Removal | Surgical − DMM + MM | No effect | No effect | Global | Mouse | |
| Potential effect of direction of gene modulation, model or tissue specificity | ||||||||
| RHEB | 29991473 | Knockout | Removal | Collagenase | Protective | Detrimental | Macrophage | Mouse |
| 31229684 | Overexpression | Overexpression | Surgical − DMM | Protective | Protective | Articular cartilage | Mouse | |
Examples of gene perturbations in animal models of OA with disagreements in the inferred gene effect are shown.
ACLT, anterior cruciate ligament transection; DMM, destabilisation of the medial meniscus; MCL, medial collateral ligament; MM, medial meniscectomy; MML, medial meniscotibial ligament.