Abstract
For the past 60 years, glucocorticosteroid (GC) drugs, including prednisone and dexamethasone (Dex), have been used for the treatment of early stage osteoarthritis (OA). However, multiple administration of GCs may destroy the articular cartilage. It has been previously reported that GC treatment may also lead to the initiation of autophagy, which is an essential mechanism for cell homeostasis and survival. Rapamycin (Rapa), an inhibitor of the mammalian target of Rapamycin, may cause a degeneration-associated pathology in organs and induce autophagy in a variety of cell types, which has been applied in the treatment of experimental OA. A previous study by our group observed that GC apparently increases the apoptosis of chondrocytes, resulting in the inhibition of extracellular matrix synthesis. Therefore, the present study aimed to further examine the effects of autophagy in chondrocytes under GC treatment and to verify the molecular mechanisms involved in the cytoprotective role of Rapa. Short-term GC treatment did not significantly inhibit chondrocyte viability, while cell autophagy was increased. In addition, upregulation of autophagy by Rapa prevented the expression of apoptosis-associated genes and improved cell activity. In conclusion, the present study revealed that increased autophagy is an adaptive response to protect chondrocytes from short‑term GC exposure, whereas prolonged GC treatment decreases autophagy and increases apoptosis in vitro. Upregulation of autophagy by Rapa may protect chondrocytes against the adverse effect induced by GC.