As the major reason for limb dysfunction, osteoarthritis (OA) is closely correlated with the level of cellular autophagy. PI3K/Akt is a classical signaling pathway which regulates autophagy, but with unclear roles in OA related cartilage injury. Studying PI3K/Akt induced autophagy in rat knee joint cartilage injury and possible functional mechanism is of critical importance for clinical treatment. This study established a rat knee joint cartilage injury model, in which Akt agonist IGF-1 or autophagy inducer Rapamycin was administrated. Western blot was used to detect the expression level of AKT, phosphorylated AKT, Beclin-1 and LC3-II/I. Formation of autophagosome and lysosome was assessed by transmission electron microscopy. HE, safranin O and toluidine blue staining was used to evaluate cartilage injury. TUNEL staining was performed to measure cell apoptosis. Real-time quantitative PCR measured the expression of cartilage injury indexes such as Aggrecan, Collagen II and MMP13. Compared with normal group, iodacetic acid treatment group showed cartilage injury, whereas AKT activation and autophagy induction groups had significant improvement. mRNA analysis showed enhanced degradation of Aggrecan and Collagen II in AKT activation and autophagy groups with decreased MMP13 mRNA level (P<0.05). Western blot results showed that after AKT activation and autophagy induction, protein levels of Beclin-1 and LC3-II/I were remarkably elevated (P<0.05). TUNEL assay showed significant inhibition of cell apoptosis. In conclusion, activation of PI3K/Akt signal pathway can improve iodacetic acid induced rat knee joint cartilage injury through inducing cell autophagy.
Keywords: Osteoarthritis cartilage injury; PI3K/Akt signaling pathway; cell autophagy.