Chaperonin 60 sustains osteoblast autophagy and counteracts glucocorticoid aggravation of osteoporosis by chaperoning RPTOR

Cell Death & Disease
Wei-Shiung LianFeng-Sheng Wang

Abstract

Glucocorticoid excess medication interrupts osteoblast homeostasis and exacerbates bone mass and microstructure loss ramping up the pathogenesis of osteoporotic disorders. Heat shock protein 60 (HSP60) is found to maintain protein function within cellular microenvironment upon encountering detrimental stress. In this study, we revealed that supraphysiological dexamethasone decreased HSP60 expression along with deregulated autophagy in osteoblasts cultures. This chaperonin is required to sustain autophagic markers Atg4, and Atg12 expression, LC3-II conversion, and autophagic puncta formation, and alleviated the glucocorticoid-induced loss of osteogenic gene expression and mineralized matrix accumulation. Regulator-associated protein of mTOR complex 1 (RPTOR) existed in HSP60 immunoprecipitate contributing to the HSP60-promoted autophagy and osteogenesis because knocking down RPTOR impaired autophagic influx and osteogenic activity. HSP60 shielded from RPTOR dysfunction by reducing the glucocorticoid-induced RPTOR de-phosphorylation, aggregation, and ubiquitination. In vivo, forced RPTOR expression attenuated the methylprednisolone-induced loss of osteoblast autophagy, bone mass, and trabecular microstructure in mice. HSP60 trans...Continue Reading

References

Jan 8, 2013·Cellular Signalling·Alejandro ParralesAna María López-Colomé
Feb 15, 2013·The New England Journal of Medicine·Augustine M K ChoiBeth Levine
Jan 25, 2014·Arthritis Research & Therapy·Isabelle AllaeysPatrice E Poubelle
Mar 14, 2014·The Lancet. Diabetes & Endocrinology·Markus J SeibelHong Zhou
Nov 12, 2014·Nature Reviews. Rheumatology·René Rizzoli, Emmanuel Biver
Dec 9, 2014·Autophagy·Marie NolletValérie Pierrefite-Carle
Apr 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shahar NisemblatAbdussalam Azem
Jun 17, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Karuna K VuppalapatiAndrei S Chagin
Sep 4, 2015·PLoS Genetics·Jianwen DengJane Y Wu
Nov 10, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Denise ToscaniNicola Giuliani
Nov 26, 2015·Nature·Laura CinqueCarmine Settembre
Feb 5, 2016·Physiological Reviews·Kerstin HartmannJan P Tuckermann
Mar 2, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lynn S MirigianSergey Leikin
Apr 7, 2016·Annual Review of Biochemistry·Andrija FinkaPierre Goloubinoff
Apr 28, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jih-Yang KoFeng-Sheng Wang
Oct 28, 2016·Nature Communications·Emanuel BergerDirk Haller
Dec 25, 2016·Biochemical and Biophysical Research Communications·Soh YamamotoShin-Ichi Yokota
Jan 11, 2017·Molecular and Cellular Biology·Stephen FitterAndrew C W Zannettino
Jan 29, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Feng-Sheng WangJih-Yang Ko
Feb 16, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Siripat AluksanasuwanVisith Thongboonkerd
May 2, 2017·Cell Chemical Biology·Katja WiechmannOliver Werz
Jun 20, 2017·The Journal of Clinical Investigation·Kyu Sang JoengBrendan H Lee

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Citations

Jun 9, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuehua YangLeisheng Jiang
Apr 23, 2020·International Journal of Molecular Sciences·Viviana di GiacomoSilvia Sancilio
Jul 16, 2020·International Journal of Molecular Sciences·Yu-Shan ChenFeng-Sheng Wang
Aug 23, 2020·Nutrients·Thanusha GanesanMohammed Abdullah Alshawsh
Jun 15, 2020·Ageing Research Reviews·Xu LiLing Qin
Apr 6, 2021·Journal of Bone and Mineral Metabolism·Haojie WuJianming Hou
Jul 4, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Yi-Zhong WangHui Wang

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Methods Mentioned

BETA
electrophoresis
ubiquitination
immunoprecipitation
transfection
PCR
Fluorescence
dissect
X-ray

Software Mentioned

Zeiss Inverted microscopy
SKYSCAN CT - Analysis

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