Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation
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, b...
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Forum Multimedia Publishing LLC
2025-04-01
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| Series: | European Cells & Materials |
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| Online Access: | https://www.ecmjournal.org/papers/vol050/vol050a07.php |
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| author | X You LQ Wu LL Fu QQ Wu BR Qi |
| author_facet | X You LQ Wu LL Fu QQ Wu BR Qi |
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| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8df45428b3834ea49bf4e9cfc84e6a4b |
| institution | Kabale University |
| issn | 1473-2262 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Forum Multimedia Publishing LLC |
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| series | European Cells & Materials |
| spelling | doaj-art-8df45428b3834ea49bf4e9cfc84e6a4b2025-08-20T03:53:12ZengForum Multimedia Publishing LLCEuropean Cells & Materials1473-22622025-04-015010912310.22203/eCM.v050a07Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradationX YouLQ WuLL FuQQ WuBR QiBackground: 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.https://www.ecmjournal.org/papers/vol050/vol050a07.phposteoarthritisampkanterior cruciate ligament transectionchondrocytessirtuin 1 |
| spellingShingle | X You LQ Wu LL Fu QQ Wu BR Qi Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation European Cells & Materials osteoarthritis ampk anterior cruciate ligament transection chondrocytes sirtuin 1 |
| 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 |
| title_full | Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation |
| title_fullStr | Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation |
| title_full_unstemmed | Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation |
| title_short | Nano-encapsulated active protein AMPK inhibits cartilage matrix degradation in experimental osteoarthritis rats via SIRT1-regulated nexilin expression nano-AMPK inhibits cartilage matrix degradation |
| title_sort | nano encapsulated active protein ampk inhibits cartilage matrix degradation in experimental osteoarthritis rats via sirt1 regulated nexilin expression nano ampk inhibits cartilage matrix degradation |
| topic | osteoarthritis ampk anterior cruciate ligament transection chondrocytes sirtuin 1 |
| url | https://www.ecmjournal.org/papers/vol050/vol050a07.php |
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