IGF-1 induces cellular senescence in rat articular chondrocytes via Akt pathway activation.

Cellular senescence decreases cell proliferation over time and is characterized by typical markers, including larger cell volume, a flattened morphology, irreversible cell cycle arrest, augmentation of senescence-associated β-galactosidase (SA-β-gal) activity and senescence-associated secretory phenotype. A variety of factors are implicated in the process of cellular aging, which mediates an organisms' lifespan. Insulin-like growth factor-1 (IGF-1) serves an essential role in regulating cell growth, division, proliferation and senescence. In the present study, the role of IGF-1 and the downstream Akt signaling pathway in rat articular chondrocyte senescence was assessed. The results of the current study demonstrated that IGF-1 promoted cellular senescence in rat articular chondrocytes via activation of SA-β-gal and the upregulation of p53 and p21 mRNA and protein levels. IGF-1 enhanced Akt phosphorylation and treatment with Akt inhibitor, MK-2206, significantly suppressed the induction of these markers. Overall, the results indicated the involvement of IGF-1 and Akt in senescence exhibited by rat articular chondrocytes.