Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis
Abstract Background Osteoarthritis (OA), the most prevalent joint disorder, is characterized by a complex etiology and a lack of safe and effective therapeutic interventions. Emerging evidence suggests that immune cell dysregulation plays a pivotal role in the pathogenesis of OA. Recent advancements...
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03543-3 |
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| author | Yong Fu Jiahui Hou Qinmeng Yang Yanpeng Lin Nie Rui Jun Wang Hangtian Wu Bin Yu |
| author_facet | Yong Fu Jiahui Hou Qinmeng Yang Yanpeng Lin Nie Rui Jun Wang Hangtian Wu Bin Yu |
| author_sort | Yong Fu |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA), the most prevalent joint disorder, is characterized by a complex etiology and a lack of safe and effective therapeutic interventions. Emerging evidence suggests that immune cell dysregulation plays a pivotal role in the pathogenesis of OA. Recent advancements in high-throughput sequencing technologies, along with the integration of machine learning into medical research, have provided novel insights into the molecular mechanisms underlying various diseases. However, the specific roles and mechanisms of immune-related factors in OA remain poorly understood. This study aims to identify potential biomarkers for the diagnosis and monitoring of OA progression and to explore targeted therapeutic strategies based on key genes associated with the disease. Results WGCNA and immune infiltration analysis identified SIK1 as a core gene involved in immune regulation during the progression of OA. In vitro experiments demonstrated that AICAR, an activator of SIK1, significantly suppressed inflammatory responses by modulating glucose and lipid metabolism in macrophages. A novel nanoliposome composite hydrogel, Gel@Lipo@AICAR, has been successfully developed for the targeted delivery of AICAR. The intra-articular administration of Gel@Lipo@AICAR demonstrated excellent biosafety and therapeutic potential in mitigating the progression of OA. Conclusions This study identifies SIK1 as a novel biomarker for diagnosing and monitoring the progression of OA. The anti-inflammatory effects of its agonist, AICAR, were validated, underscoring its role in reprogramming macrophage glucose and lipid metabolism. Furthermore, the development of Gel@Lipo@AICAR, a nanoliposome composite hydrogel, presents a promising therapeutic strategy for the treatment of OA. Graphical Abstract Preparation of Gel@Lipo@AICAR and therapeutic efficacy in ACLT osteoarticular model mice |
| format | Article |
| id | doaj-art-c3e4efc6678a4d258d9798c7dd82ce07 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-c3e4efc6678a4d258d9798c7dd82ce072025-08-20T04:01:41ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112110.1186/s12951-025-03543-3Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritisYong Fu0Jiahui Hou1Qinmeng Yang2Yanpeng Lin3Nie Rui4Jun Wang5Hangtian Wu6Bin Yu7Trauma Center, Hand and Foot Surgery, Paediatric Orthopedic Department, The Second Affiliated Hospital, University of South ChinaDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical UniversityDepartment of Foot and Ankle Surgery, Guangzhou Orthopedic HospitalDepartment of Radiology, Nanfang Hospital, Southern Medical UniversityDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical UniversitySchool of Animal Science and Technology, Foshan UniversityDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical UniversityDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical UniversityAbstract Background Osteoarthritis (OA), the most prevalent joint disorder, is characterized by a complex etiology and a lack of safe and effective therapeutic interventions. Emerging evidence suggests that immune cell dysregulation plays a pivotal role in the pathogenesis of OA. Recent advancements in high-throughput sequencing technologies, along with the integration of machine learning into medical research, have provided novel insights into the molecular mechanisms underlying various diseases. However, the specific roles and mechanisms of immune-related factors in OA remain poorly understood. This study aims to identify potential biomarkers for the diagnosis and monitoring of OA progression and to explore targeted therapeutic strategies based on key genes associated with the disease. Results WGCNA and immune infiltration analysis identified SIK1 as a core gene involved in immune regulation during the progression of OA. In vitro experiments demonstrated that AICAR, an activator of SIK1, significantly suppressed inflammatory responses by modulating glucose and lipid metabolism in macrophages. A novel nanoliposome composite hydrogel, Gel@Lipo@AICAR, has been successfully developed for the targeted delivery of AICAR. The intra-articular administration of Gel@Lipo@AICAR demonstrated excellent biosafety and therapeutic potential in mitigating the progression of OA. Conclusions This study identifies SIK1 as a novel biomarker for diagnosing and monitoring the progression of OA. The anti-inflammatory effects of its agonist, AICAR, were validated, underscoring its role in reprogramming macrophage glucose and lipid metabolism. Furthermore, the development of Gel@Lipo@AICAR, a nanoliposome composite hydrogel, presents a promising therapeutic strategy for the treatment of OA. Graphical Abstract Preparation of Gel@Lipo@AICAR and therapeutic efficacy in ACLT osteoarticular model micehttps://doi.org/10.1186/s12951-025-03543-3WGCNASIK1AICARMacrophage metabolismNanoliposome composite hydrogelOsteoarthritis |
| spellingShingle | Yong Fu Jiahui Hou Qinmeng Yang Yanpeng Lin Nie Rui Jun Wang Hangtian Wu Bin Yu Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis Journal of Nanobiotechnology WGCNA SIK1 AICAR Macrophage metabolism Nanoliposome composite hydrogel Osteoarthritis |
| title | Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis |
| title_full | Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis |
| title_fullStr | Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis |
| title_full_unstemmed | Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis |
| title_short | Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis |
| title_sort | liposome encapsulated aicar hydrogel regulates macrophage metabolic reprogramming via sik1 activation to alleviate osteoarthritis |
| topic | WGCNA SIK1 AICAR Macrophage metabolism Nanoliposome composite hydrogel Osteoarthritis |
| url | https://doi.org/10.1186/s12951-025-03543-3 |
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