Decreased Autophagy Level in Tibial Plateau Chondrocytes Causes Increased Apoptosis of Chondrocytes in Spontaneous Osteoarthritis of Guinea Pigs

Abstract

Background: To observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. Methods: Fifty 2-month-old female Hartley guinea pigs were divided into a normal group, which was euthanized after 7 months, and an OA group, ten of which were euthanized after 10 months. Immunohistochemistry, PCR and western blotting were used to evaluate the level of autophagy, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group and a 3-MA group. Intracellular glycogen accumulation and chondrocyte apoptosis were observed by changing the level of autophagy in chondrocytes in vivo. Findings: When spontaneous OA occurred in the guinea pigs, the level of autophagy in tibial plateau chondrocytes decreased,and intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the autophagy level of tibial plateau chondrocytes in OA guinea pigs, the intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased. When the autophagy level of the chondrocytes was weakened, intracellular glycogen accumulation was further increased, and the apoptosis rate was higher. Interpretation: The autophagy function of chondrocytes may be at least partly involved in the catabolism of glycogen in chondrocytes. In OA guinea pigs, the autophagy level in tibial plateau chondrocytes decreased, and the chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for the chondrocytes and increased apoptosis. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (no. 81572098), Natural Science Foundation of Shanxi Province of China (no.201701D121161) and Key Research and Development Projects of Shanxi Province (no.201803D31160). Declaration of Interests: None declared. Ethics Approval Statement: This study was approved by the Ethics Committee of Shanxi Medical University (approval number: SXMUE2019004). All experiments were performed in accordance with the Public Health Service Policy and the Guide to the Care and Use of Laboratory Animals.