Rapamycin protects chondrocytes against IL-18-induced apoptosis and ameliorates rat osteoarthritis

• DOI: 10.18632/aging.102937
• Publication Date: 2020-03-17T19:51:18Z
• Authors: Jiapeng Bao; Zhonggai Chen; Langhai Xu; Lidong Wu; Yan Xiong
• Keywords: Inflammation; Male; Sirolimus; 0303 health sciences; Interleukin-18; Apoptosis; Rats; 3. Good health; Rats, Sprague-Dawley; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Chondrocytes; Osteoarthritis; Autophagy; Animals; Immunosuppressive Agents; Research Paper; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction

Interleukin 18 (IL-18) promotes inflammation and apoptosis in chondrocytes, thereby contributing to the development progression of osteoarthritis (OA). Here, we investigated effects IL-18 treatment inhibition rat chondrocytes vitro vivo. We used RT-PCR Western blotting measure mRNA protein levels chondrocyte-specific genes Collagen II Aggrecan as well apoptosis-related (Bax, Bcl2, Caspase3/9), autophagy-related (Atg5, Atg7, Beclin1, LC3), mTOR pathway-related (PI3K, Akt, mTOR). observed a decrease levels, upregulation chondrocyte apoptosis, downregulation autophagy, activation PI3K/Akt/mTOR pathway upon treatment. tests using 740Y-P (PI3K activator), SC79 (AKT 3BDO (mTOR or LY294002 inhibitor) revealed that enhances gene degradation induced by IL-18, while its has protective on chondrocytes. also found with rapamycin (a selective exerts chondro-protective ameliorate OA promoting autophagy. These results suggest could be exploited for therapeutic benefits OA.