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

Osteoarthritis and Cartilage
Stefania D'AdamoM Lotz

Abstract

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

References

Dec 1, 1994·The Journal of Clinical Investigation·M B GoldringJ F Apperley
Mar 28, 1998·The Journal of Biological Chemistry·T Noda, Y Ohsumi
Jun 8, 2001·MMWR. Morbidity and Mortality Weekly Report·UNKNOWN Centers for Disease Control and Prevention (CDC)
Apr 1, 1959·Arthritis and Rheumatism·E NETTELBLADT, L SUNDBLAD
Apr 8, 2004·Developmental Cell·Beth Levine, Daniel J Klionsky
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Aug 8, 2007·Annals of Internal Medicine·David J Hunter
Sep 6, 2007·Journal of Cellular Physiology·Mary B Goldring, Steven R Goldring
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
Jan 20, 2010·FEBS Letters·Chang Hwa JungDo-Hyung Kim
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Mariola Kurowska-StolarskaIain B McInnes
Aug 3, 2011·Nature Reviews. Rheumatology·Martin K Lotz, Beatriz Caramés
Dec 8, 2011·Arthritis and Rheumatism·Hiroshi SasakiRyosuke Kuroda
Jan 12, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·YuXiang FangLing Tian
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun
Dec 4, 2012·Histochemistry and Cell Biology·Clara L OesteDolores Pérez-Sala
Apr 23, 2013·Arthritis and Rheumatism·Beatriz CaramésMartin K Lotz
Jul 10, 2013·Current Drug Targets·Hugo SecaM Helena Vasconcelos
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Jens FüllgrabeBertrand Joseph
Dec 18, 2013·Autophagy·Sahana HollaKithiganahalli Narayanaswamy Balaji
Dec 20, 2013·International Journal of Molecular Sciences·Xiaochuan LiFei Wang
Sep 5, 2014·Arthritis & Rheumatology·Yukio AkasakiMartin K Lotz
Oct 18, 2014·Arthritis & Rheumatology
Feb 25, 2015·Arthritis & Rheumatology·Beatriz CaramésMartin K Lotz

❮ Previous
Next ❯

Citations

Oct 8, 2016·Autophagy·Lisa B FrankelAnders H Lund
Nov 16, 2016·Biomolecules·Panagiota PapanagnouMaria Tsironi
Dec 22, 2016·International Journal of Molecular Sciences·Edith CharlierDominique De Seny
Jul 13, 2016·Current Rheumatology Reports·Gregory R Sondag, Tariq M Haqqi
Nov 8, 2017·Oxidative Medicine and Cellular Longevity·Wen LiDu Feng
Apr 12, 2020·Molecular Biology Reports·Aynaz MihanfarMohammad Nouri
Jan 13, 2017·BioMed Research International·Tianyang GaoQuanyi Guo
Oct 18, 2016·Current Opinion in Rheumatology·Yolande F M Ramos, Ingrid Meulenbelt
Aug 10, 2017·Journal of Neuropathology and Experimental Neurology·Fengyan ZhaoDezhi Mu
Jul 11, 2018·Frontiers in Physiology·Claire VinatierBeatriz Caramés
Jul 18, 2017·Oxidative Medicine and Cellular Longevity·Stefania D'AdamoFlavio Flamigni
Jun 18, 2019·BioMed Research International·Yinghao Yu, Jijun Zhao
Jul 1, 2020·Cellular and Molecular Life Sciences : CMLS·Abazar EsmaeiliMohamadreza Baghaban Eslaminejad
Jan 13, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Wenqi GuHongtao Zhang
Dec 17, 2020·Frontiers in Cell and Developmental Biology·Ran DuanZheng-Zhao Liu
Apr 4, 2021·Antioxidants·Yohei SanadaShigeru Miyaki
Jul 3, 2021·Frontiers in Physiology·Maria Eugenia Vázquez-MosqueraFrancisco J Blanco
Jul 19, 2021·Tissue Engineering and Regenerative Medicine·Liu HuiZhou Yong

❮ Previous
Next ❯

Related Concepts

Related Feeds

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.