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.