Hailin Deng , Wanlan Liu , Liang Xiang, Junxing Wu
{"title":"HNRNPA1促进TRIM37 mRNA稳定性,介导TRAF6泛素化,缓解骨关节炎","authors":"Hailin Deng , Wanlan Liu , Liang Xiang, Junxing Wu","doi":"10.1016/j.intimp.2025.115568","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA), characterized by progressive cartilage degeneration, involves inflammation and dysregulated cell death. The functional role of the RNA-binding protein HNRNPA1 via TRIM37-mediated TRAF6 ubiquitination in OA pathogenesis remains unclear.</div></div><div><h3>Methods</h3><div>Using a destabilization of the medial meniscus (DMM)-induced OA mouse model, we assessed cartilage histopathology, inflammation, and expression of HNRNPA1, TRIM37, and TRAF6. Interleukin-1β (IL-1β)-treated chondrocytes were analyzed for viability, apoptosis, pyroptosis, and extracellular matrix (ECM) synthesis. Mechanistic studies included RNA-fluorescence in situ hybridization (RNA-FISH), RNA immunoprecipitation (RIP), mRNA stability assays, and co-immunoprecipitation (Co-IP) following TRIM37 knockdown to examine TRAF6 ubiquitination.</div></div><div><h3>Results</h3><div>OA progression correlated with decreased HNRNPA1 and TRIM37 but increased TRAF6 expression. HNRNPA1 overexpression mitigated cartilage degradation, inflammation, and autophagy impairment. Mechanistically, HNRNPA1 stabilized TRIM37 mRNA, thereby enhancing TRIM37-mediated TRAF6 ubiquitination. This cascade suppressed pyroptosis while activating autophagy, conferring chondroprotection.</div></div><div><h3>Conclusion</h3><div>The HNRNPA1/TRIM37/TRAF6 axis regulates the balance between autophagy and pyroptosis, offering a novel therapeutic target to alleviate OA.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"166 ","pages":"Article 115568"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"HNRNPA1 promotes TRIM37 mRNA stability and mediates TRAF6 ubiquitination to alleviate osteoarthritis\",\"authors\":\"Hailin Deng , Wanlan Liu , Liang Xiang, Junxing Wu\",\"doi\":\"10.1016/j.intimp.2025.115568\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Osteoarthritis (OA), characterized by progressive cartilage degeneration, involves inflammation and dysregulated cell death. The functional role of the RNA-binding protein HNRNPA1 via TRIM37-mediated TRAF6 ubiquitination in OA pathogenesis remains unclear.</div></div><div><h3>Methods</h3><div>Using a destabilization of the medial meniscus (DMM)-induced OA mouse model, we assessed cartilage histopathology, inflammation, and expression of HNRNPA1, TRIM37, and TRAF6. Interleukin-1β (IL-1β)-treated chondrocytes were analyzed for viability, apoptosis, pyroptosis, and extracellular matrix (ECM) synthesis. Mechanistic studies included RNA-fluorescence in situ hybridization (RNA-FISH), RNA immunoprecipitation (RIP), mRNA stability assays, and co-immunoprecipitation (Co-IP) following TRIM37 knockdown to examine TRAF6 ubiquitination.</div></div><div><h3>Results</h3><div>OA progression correlated with decreased HNRNPA1 and TRIM37 but increased TRAF6 expression. HNRNPA1 overexpression mitigated cartilage degradation, inflammation, and autophagy impairment. Mechanistically, HNRNPA1 stabilized TRIM37 mRNA, thereby enhancing TRIM37-mediated TRAF6 ubiquitination. This cascade suppressed pyroptosis while activating autophagy, conferring chondroprotection.</div></div><div><h3>Conclusion</h3><div>The HNRNPA1/TRIM37/TRAF6 axis regulates the balance between autophagy and pyroptosis, offering a novel therapeutic target to alleviate OA.</div></div>\",\"PeriodicalId\":13859,\"journal\":{\"name\":\"International immunopharmacology\",\"volume\":\"166 \",\"pages\":\"Article 115568\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International immunopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1567576925015590\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925015590","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
HNRNPA1 promotes TRIM37 mRNA stability and mediates TRAF6 ubiquitination to alleviate osteoarthritis
Background
Osteoarthritis (OA), characterized by progressive cartilage degeneration, involves inflammation and dysregulated cell death. The functional role of the RNA-binding protein HNRNPA1 via TRIM37-mediated TRAF6 ubiquitination in OA pathogenesis remains unclear.
Methods
Using a destabilization of the medial meniscus (DMM)-induced OA mouse model, we assessed cartilage histopathology, inflammation, and expression of HNRNPA1, TRIM37, and TRAF6. Interleukin-1β (IL-1β)-treated chondrocytes were analyzed for viability, apoptosis, pyroptosis, and extracellular matrix (ECM) synthesis. Mechanistic studies included RNA-fluorescence in situ hybridization (RNA-FISH), RNA immunoprecipitation (RIP), mRNA stability assays, and co-immunoprecipitation (Co-IP) following TRIM37 knockdown to examine TRAF6 ubiquitination.
Results
OA progression correlated with decreased HNRNPA1 and TRIM37 but increased TRAF6 expression. HNRNPA1 overexpression mitigated cartilage degradation, inflammation, and autophagy impairment. Mechanistically, HNRNPA1 stabilized TRIM37 mRNA, thereby enhancing TRIM37-mediated TRAF6 ubiquitination. This cascade suppressed pyroptosis while activating autophagy, conferring chondroprotection.
Conclusion
The HNRNPA1/TRIM37/TRAF6 axis regulates the balance between autophagy and pyroptosis, offering a novel therapeutic target to alleviate OA.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.