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Chondroprotective effects of Apolipoprotein D in knee osteoarthritis mice through the PI3K/AKT/mTOR signaling pathway.

Authors :
Zhang G
Huang C
Wang R
Guo J
Qin Y
Lv S
Source :
International immunopharmacology [Int Immunopharmacol] 2024 May 30; Vol. 133, pp. 112005. Date of Electronic Publication: 2024 Apr 15.
Publication Year :
2024

Abstract

Background: Because the pathophysiology of osteoarthritis (OA) has not been fully elucidated, targeted treatments are lacking. In this study, we assessed the role and underlying mechanism apolipoprotein D (APOD) on the development of OA.<br />Methods: To establish an in vitro OA model, we extracted primary chondrocytes from the cartilage of C57BL/6 mice and stimulated the chondrocytes with IL-1β. After APOD intervention or incubation with an overexpressing plasmid, we detected inflammatory-related markers using RT-qPCR, Western blotting, and ELISA. To detect apoptosis and autophagy-related markers, we used flow cytometry, immunofluorescence, and transmission electron microscopy (TEM). Finally, we measured the level of oxidative stress. We also used RNA-seq to identify the APOD-regulated downstream signaling pathways. We used an in vivo mice OA model of the anterior cruciate ligament transection (ACLT) and administered intra-articular adenovirus overexpressing APOD. To examine cartilage damage severity, we used immunohistochemical analysis (IHC), micro-CT, scanning electron microscopy (SEM), and Safranin O-fast green staining.<br />Results: Our results showed that APOD inhibited chondrocyte inflammation, degeneration, and apoptosis induced by IL-1β. Additionally, APOD reversed autophagy inhibition and oxidative stress and also blocked activation of the PI3K/AKT/mTOR signaling pathway induced by IL-1β. Finally, overexpression of the APOD gene through adenovirus was sufficient to mitigate OA progression.<br />Conclusions: Our findings revealed that APOD had a chondroprotective role in OA progression by the PI3K/AKT/mTOR signaling pathway.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1878-1705
Volume :
133
Database :
MEDLINE
Journal :
International immunopharmacology
Publication Type :
Academic Journal
Accession number :
38626543
Full Text :
https://doi.org/10.1016/j.intimp.2024.112005