SCD1 deficiency exacerbates osteoarthritis by inducing ferroptosis in chondrocytes

2023 Annals of Translational Medicine. All rights reserved..

Background: Osteoarthritis (OA) is a severe joint disease that causes cartilage destruction and mobility loss. Abnormal fatty acid metabolism of chondrocytes plays a role in OA development. Stearoyl-CoA desaturase (SCD1) is a rate-limiting enzyme in the anabolism of unsaturated fatty acids. This study aimed to investigate the role of the SCD1 protein in the degenerative process of OA.

Methods: The GSE176199 gene expression profile dataset was analyzed by Gene Set Enrichment Analysis (GSEA). An animal model of OA was established using C57BL/6J wild-type (WT) (n=40) and SCD1 knockout (SCD1-KO) (n=20) mice. The histological scoring method of the Osteoarthritis Research Society International (OARSI) was used to quantify the degree of cartilage degeneration. The expression of SCD1 protein and relevant ferroptosis indicators were evaluated.

Results: The GSEA analysis showed that unsaturated fatty acid synthesis was inhibited in human OA chondrocytes. Meanwhile, the expression of SCD1 protein was significantly reduced in human OA articular cartilage. SCD1-KO mice exhibited early OA and accelerated cartilage loss after destabilization of medial meniscus (DMM)-induced OA. Furthermore, we found that the SCD1-PPARG axis regulates articular cartilage homeostasis via a mechanism involving the induction of ferroptosis-related gene expression in ATDC5 chondrocytes.

Conclusions: SCD1 deficiency exacerbates OA by inducing ferroptosis in chondrocytes.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

Annals of translational medicine - 11(2023), 4 vom: 28. Feb., Seite 171

Sprache:

Englisch

Beteiligte Personen:

Yu, Chao [VerfasserIn]
Yang, Xian [VerfasserIn]
Jiang, Qingsong [VerfasserIn]
Liu, Zhibo [VerfasserIn]
Chen, Yan [VerfasserIn]
Zang, Guangchao [VerfasserIn]
Huang, Wei [VerfasserIn]

Links:

Volltext

Themen:

Articular cartilage
Ferroptosis
Journal Article
Monounsaturated fatty acids
Osteoarthritis (OA)
Stearoyl-CoA desaturases

Anmerkungen:

Date Revised 16.03.2023

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.21037/atm-22-6630

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM354286153