Changes in mature meniscus by FoxO knockout and FoxO overexpression. (A) Gene expression in AcanCreERT2-FoxO TKO mice at 6 mo old: FoxO genes (FoxO1, FoxO3, and FoxO4), meniscus-specific genes (Col1a1, Col2a1, Acan, Comp, Prg4, Mkx, Sox5, and Sox9), hypertrophy genes (Runx2, Col10a1, and Mmp13), antioxidant defense genes (Sesn1, Sesn3, and Gpx3), autophagy genes (Map1lc3b, Becn1, Gabarapl1, Bnip3, and Prkaa2), and redox regulation (Catalase, Sod2, and Txnip). Relative gene expression was normalized by expression values of each gene in comparison between data from AcanCreERT2 TKO mice littermate AcanCreERT2-negative mice that also received tamoxifen injections. RNA was collected from 6-mo-old mice (medial and lateral menisci from both joints of each mouse were pooled) for qRT-PCR analysis (n = 6 mice per group, *P < 0.05). (B) Cells from human OA menisci were transduced with adenovirus encoding FoxO1-AAA, a constitutively active form of FoxO1. RNA was collected after 48 h for qRT-PCR analysis (n = 6 per group, *P < 0.05).