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Oleic and linoleic acids promote chondrocyte apoptosis by inhibiting autophagy via downregulation of SIRT1/FOXO1 signaling.

Authors :
Li, Xiaodong
Zhao, Chen
Mao, Chuanyuan
Sun, Guantong
Yang, Fei
Wang, Lei
Wang, Xiaoqing
Source :
BBA: Molecular Basis of Disease. Apr2024, Vol. 1870 Issue 4, pN.PAG-N.PAG. 1p.
Publication Year :
2024

Abstract

Osteoarthritis (OA) is a complex joint disease that currently has no cure. OA involves metabolic disorders in chondrocytes and an imbalance between autophagy and apoptosis. As a common risk factor for OA, obesity induces changes in the fatty acid composition of synovial fluid, thereby disturbing chondrocyte homeostasis. However, whether unsaturated fatty acids affect the development of OA by regulating chondrocyte autophagy remains unclear. This study aimed to determine the effects of oleic and linoleic acids on chondrocyte autophagy and related mechanisms. Based on the mass spectrometry results, the levels of multiple unsaturated fatty acids, including oleic and linoleic acids, in the synovial fluid of patients with OA and obesity were significantly higher than those in patients with OA only. Moreover, we found that FOXO1 and SIRT1 were downregulated after oleic and linoleic acids treatment of chondrocytes, which inhibited chondrocyte autophagy. Importantly, the upregulation of SIRT1 and FOXO1 expression not only increased the level of autophagy but also improved the expression of chondrocyte extracellular matrix proteins. Furthermore, upregulated SIRT1 and FOXO1 expression alleviated the destruction of the articular cartilage in an OA rat model. Our results suggest that SIRT1/FOXO1 signaling can alleviate oleic acid- and linoleic acid-induced cartilage degradation both in vitro and in vivo and that the SIRT1/FOXO1 pathway may serve as an effective treatment target for inhibiting OA progression. • OLA and LA increase significantly in the SF of patients with OA and obesity. • OLA and LA affect the development of OA by regulating chondrocyte autophagy. • OLA and LA affect chondrocyte autophagy by downregulation of SIRT1/FOXO1 signaling. • Upregulated SIRT1 and FOXO1 alleviate OLA- and LA-induced cartilage degradation. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09254439
Volume :
1870
Issue :
4
Database :
Academic Search Index
Journal :
BBA: Molecular Basis of Disease
Publication Type :
Academic Journal
Accession number :
176432141
Full Text :
https://doi.org/10.1016/j.bbadis.2024.167090