Upregulation of P63 inhibits chondrocyte autophagy thereby enhancing the malignant progression of osteoarthritis

作者：Wangyang, Yufan; Zheng, Xin; Liu, Guang-wang; Li, Dong-ya; Feng, Yan-bo; Guo, Tong-ya; Ma, Chao; Wang, Tao^*

来源：Pharmazie, 2017, 72(6): 361-364.

DOI：10.1691/ph.2017.6933

• CELL-DEATH
• EXPRESSION
• MICRORNA
• PATHOGENESIS
• CARTILAGE
• SENESCENCE
• CARCINOMA
• PROGNOSIS

Loss of autophagy is suggested to play a key role in the progression of osteoarthritis (OA). P63 is a member of the P53 family, which is widely dysregulated in various tumors. However, the specific role of P63 in chondrocyte autophagy has never been fully understood. Here, the expression level of P63 in the articular cartilages of OA patients and chondrocytes treated with 3-MA was explored using western blot. Autophagy was determined using transmission electron microscopy and mRFP-GFP-LC3 assay. Fewer autophagic vesicles were identified in the articular cartilages of OA patients compared with that of normal control. Both the mRNA and protein levels of P63 was markedly increased in the articular cartilages of OA patients compared with that of normal control. MT1-assay demonstrated that P63 overexpression markedly reduced chondrocyte viability at 24, 36 and 48 h, while inhibition of P63 inhibited cell viability at 24, 36 and 48 h, respectively. Furthermore, autophagic flux assay showed that transfection of ad-P63 markedly decreased the yellow dots in chondrocytes, while inhibition of P63 induced chondrycyte autophagy. In summary, we first demonstrated that upregulation of P63 in the cartilage tissues of OA patients inhibited chondrocyte autophagy thereby contributing to the malignant progression of OA.

• 出版日期2017-6
• 单位徐州医科大学