Figure 4: Accelerated OA in AMPKα1α2 conditional double knockout (AMPKα cDKO) mice with ageing.

(a) Representative photographs of articular cartilage destruction in female and male AMPKα cDKO mice and their age- and sex- matched WT littermates at 9 and 12 months of age. Sections were stained with Safranin O/Fast Green. A slight loss of proteoglycans in the superficial zone and fibrillation in articular cartilage (arrowhead) were observed in female AMPKα cDKO mice at 9 or 12 months. Loss of uncalcified cartilage and alteration of the tidemark integrity (arrow) were observed in male AMPKα cDKO mice at 9 months. Scale bars = 100 μm. (b) Representative Safranin-O/Fast green staining of knee joints from male AMPKα cDKO mice and their sex matched WT littermates at 12 months of age. Loss of the entire articular cartilage layer (black arrows), formation of osteophyte (green arrows), severe disruption of meniscal tissue (asterisk) and bone marrow-like regions in the enlarged medial collateral ligament (red arrows) were observed in male AMPKα cDKO mice at 12 months of age. T, tibia; F, femur; AC, articular cartilage; M, meniscus; MCL, medial collateral ligament. MAR, marrow cavities. Scale bars = 100 μm. (c) The OARSI scores for the medial femoral condyle and the medial tibial condyle in female and male AMPKα cDKO mice and their sex-matched WT littermates at 9 and 12 months of age (9 months old: WT females n = 5, cDKO females n = 7, WT males n = 7, cDKO males n = 9; 12 months old: WT females n = 7, cDKO females n = 8, WT males n = 8, cDKO males n = 11). (d) Representative photographs of synovitis in male AMPKα cDKO mice and their sex-matched WT littermates at 12 months of age. Sections were stained with H&E. Scale bars = 50 μm. (e) Osteophyte maturity and synovitis scores in male AMPKα cDKO mice (n = 11) and their sex-matched WT littermates (n = 8) at 12 months of age. *p < 0.05. **p < 0.01. ***p < 0.001. NS = not significant.