SIRT1 directly activates autophagy in human chondrocytes

Pradeep K Sacitharan; George Bou-Gharios; James R Edwards

doi:10.1038/s41420-020-0277-0

SIRT1 directly activates autophagy in human chondrocytes

Cell Death Discov. 2020 May 29:6:41. doi: 10.1038/s41420-020-0277-0. eCollection 2020.

Authors

Pradeep K Sacitharan^{1

2}, George Bou-Gharios², James R Edwards²

Affiliations

¹ Botnar Research Centre, University of Oxford, Oxford, OX3 7LD UK.
² The Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX UK.

Abstract

Osteoarthritis (OA) is the most common form of arthritis worldwide with no effective treatment. Ageing is the primary risk factor for OA. We sought to investigate if there is a distinct and functional convergence of ageing-related mechanisms SIRT1 and autophagy in chondrocytes. Our results show that, levels of SIRT1 are decreased in human normal aged and OA cartilage compared with young cartilage. Moreover, silencing SIRT1 in chondrocytes lead to decreased expression of chondrogenic markers but did not alter the expression of catabolic proteases. In contrast, activation of SIRT1 increased autophagy in chondrocytes by the deacetylation of lysine residues on crucial autophagy proteins (Beclin1, ATG5, ATG7, LC3). This activation was shown to be mTOR/ULK1 independent. Our results indicate that maintenance of autophagy in chondrocytes by SIRT1 is essential for preserving cartilage integrity throughout life and therefore is a target for drug intervention to protect against OA.

Keywords: Macroautophagy; Osteoarthritis.

Abstract

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