2025 Volume No 50 – pages 109-123
Title: Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation |
Authors: X You, LQ Wu, LL Fu, QQ Wu, BR Qi |
Address: Central Laboratory, Hainan Branch, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, 572000 Sanya, Hainan, China |
E-mail: bangruoqi at 126.com |
Abstract: Background: Osteoarthritis (OA) is characterized by progressive cartilage matrix degradation. Although adenosine monophosphate-activated protein kinase (AMPK) shows promise in treating OA, its clinical application is limited by poor bioavailability. Nano-encapsulation may overcome this limitation, but the underlying molecular mechanisms remain unclear. Methods: OA was induced in rats using the anterior cruciate ligament transection (ACLT) model, followed by intra-articular injection of nano-AMPK. Cartilage degradation was assessed by Masson staining and immunohistochemistry. The molecular mechanism was investigated using interleukin-1 beta (IL-1β)-induced rat chondrocytes, with or without sirtuin 1 (SIRT1) inhibitor (EX527) treatment and Nexilin silencing. The expression of cartilage matrix components, degradative enzymes, and signaling molecules was analyzed by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results: Nano-AMPK treatment significantly reduced cartilage degradation in ACLT rats, which was evidenced by increased collagen type II alpha 1 chain (COL2A1) and aggrecan expression and decreased matrix metalloproteinase (MMP)-3, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels. In vitro studies revealed that nano-AMPK protected against IL-1β-induced matrix degradation by upregulating SIRT1 and Nexilin expression. Either SIRT1 inhibition or Nexilin silencing abolished the protective effects of nano-AMPK, indicating that the SIRT1-Nexilin pathway mediates nano-AMPK’s chondroprotective effects. Conclusions: This study demonstrated that nano-encapsulated AMPK effectively prevented cartilage matrix degradation in experimental OA through a previously unidentified SIRT1-regulated Nexilin pathway, providing new insights into OA treatment strategies. |
Keywords: Osteoarthritis, AMPK, anterior cruciate ligament transection, chondrocytes, sirtuin 1. |
Publication date: 24th April 2025 |
Copyright policy: © 2025 The Author(s). Published by Forum Multimedia Publishing, LLC. This article is distributed in accordance with Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/). |
Article download: Pages 109-123 (PDF file) |
