Cathelicidin-BF regulates the AMPK/SIRT1/NF-κB pathway to ameliorate murine osteoarthritis: In vitro and in vivo studie

• Published in: International immunopharmacology 2024-06, Vol.134, p.112201, Article 112201
• Main Authors: Zhou, Hao, Zou, Linfang, Ren, Hui, Shen, Zhenyu, Lin, Yuanqu, Cai, Haikang, Zhang, Jingdong
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK/SIRT1/NF-κB pathway; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Cathelicidin-BF; Cathelicidins; Chondrocytes - drug effects; Chondrocytes - metabolism; Disease Models, Animal; Extracellular matrix degradation; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; Osteoarthritis; Osteoarthritis - drug therapy; Osteoarthritis - metabolism; Osteoarthritis - pathology; Signal Transduction - drug effects; Sirtuin 1 - genetics; Sirtuin 1 - metabolism
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112201

•Cathelicidin-BF (BF-30) can suppress IL-1β-induced inflammation and cartilage metabolic imbalance.•BF-30 can delay disease progression in a mice osteoarthritis model.•BF-30 mediates its positive cellular effects by activating the AMPK/SIRT1/NF-κB signalling pathway. Osteoarthritis (OA) is a chronic degenerative disease with a significant prevalence that causes cartilage damage and can lead to disability. The main factors contributing to the onset and progression of OA include inflammation and degeneration of the extracellular matrix. Cathelicidin-BF (BF-30), a natural peptide derived from Bungarus fasciatus venom, has shown multiple important pharmacological effects. However, the action mechanism of BF-30 in OA treatment remains to be elucidated. In this research, X-ray and Safranin O staining were employed to evaluate the imageology and histomorphology differences in the knee joints of mice in vivo. Techniques such as Western blot analysis, RT-qPCR, ELISA, and immunofluorescence staining were applied to examine gene and protein level changes in in vitro experiments. It was found that BF-30 significantly decreased inflammation and enhanced extracellular matrix metabolism. For the first time, it was demonstrated that the positive effects of BF-30 are mediated through the activation of the AMPK/SIRT1/NF-κB pathway. Moreover, when BF-30 was co-administered with Compound C, an AMPK inhibitor, the therapeutic benefits of BF-30 were reversed in both in vivo and in vitro settings. In conclusion, the findings suggest that BF-30 could be a novel therapeutic agent for OA improvement.