MicroRNA-155 suppresses autophagy in chondrocytes by modulating expression of autophagy proteins

详细信息    查看全文

• 作者：S. D'Adamo^&dagger ; ; ^&Dagger ; ; O. Alvarez-Garcia^&dagger ; ; Y. Muramatsu^&dagger ; ; F. Flamigni^&Dagger ; ; M.K. Lotz^&dagger ; ; ^{mlotz@scripps.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Autophagy ; microRNAs ; Cartilage ; Chondrocytes
• 刊名：Osteoarthritis and Cartilage
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：24
• 期：6
• 页码：1082-1091
• 全文大小：2009 K

文摘

Autophagy dysfunction has been reported in osteoarthritis (OA) cartilage. The objective of this study was to investigate the role of microRNA-155 (miR-155), which is overexpressed in OA, in the regulation of autophagy in human chondrocytes.

Design

Rapamycin (50 nM) and 2-deoxyglucose (2-DG) (5 mM) were used to stimulate autophagy in primary human articular chondrocytes and in the T/C28a2 human chondrocyte cell line. Cells were transfected with LNA GapmeR or mimic specific for miR-155 and autophagy flux was assessed by LC3 western blotting and by Cyto-ID^® dye quantification in autophagic vacuoles. Expression of predicted miR-155 targets in the autophagy pathway were analyzed by real-time PCR and western blotting.

Results

Autophagy flux induced by rapamycin and 2-DG was significantly increased by miR-155 LNA, and significantly decreased after miR-155 mimic transfection in T/C28a2 cells and in human primary chondrocytes. These effects of miR-155 on autophagy were related to suppression of gene and protein expression of key autophagy regulators including Ulk1, FoxO3, Atg14, Atg5, Atg3, Gabarapl1, and Map1lc3.

Conclusion

MiR-155 is an inhibitor of autophagy in chondrocytes and contributes to the autophagy defects in OA.