Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis
BackgroundAnkylosing spondylitis (AS) is an autoimmune disease characterized by bone destruction and abnormal remodeling. Metrnl, a secreted protein involved in inflammation and immune regulation, has recently been linked to bone growth. This study aimed to evaluate serum Metrnl levels in AS patient...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595181/full |
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| author | Zhuoqi Li Zhuoqi Li Tao Sun Min Zhao Liping Xia Hui Shen |
| author_facet | Zhuoqi Li Zhuoqi Li Tao Sun Min Zhao Liping Xia Hui Shen |
| author_sort | Zhuoqi Li |
| collection | DOAJ |
| description | BackgroundAnkylosing spondylitis (AS) is an autoimmune disease characterized by bone destruction and abnormal remodeling. Metrnl, a secreted protein involved in inflammation and immune regulation, has recently been linked to bone growth. This study aimed to evaluate serum Metrnl levels in AS patients and explore its bone regulatory mechanisms using cell models and multi-omics analyses.MethodsA total of 275 participants aged 16–60 years were included to measure serum Metrnl levels using Enzyme-Linked-Immunosorbent Assay (ELISA). Correlation and receiver operating characteristic (ROC) curve analyses assessed the diagnostic and predictive value of Metrnl. Mouse pre-osteoblastic MC3T3-E1 cells were treated with recombinant Metrnl (0/10/50 ng/mL) during 28-day osteogenic differentiation. RT-qPCR and alkaline phosphatase (ALP)/Alizarin Red S (ARS) staining was used to evaluate direct osteogenic differentiation effects. Transcriptomic and proteomic studies were conducted to further explore bone metabolism mechanisms. Finally, multi-omics integration analyses identified key pathways and targets.ResultsElevated serum Metrnl levels correlated directly with disease activity markers (CRP, ESR, IL-6) in AS-Active patients, but not in AS-Stable patients. ROC analysis validated Metrnl as a potential auxiliary diagnostic biomarker for high disease activity. In vitro, Metrnl suppressed ALP/OCN expression without altering overall osteogenic differentiation. Transcriptomic and proteomic analyses revealed Metrnl’s regulatory effects on osteogenic genes and proteins, emphasizing its role in bone and cartilage development. Bioinformatics highlighted Metrnl’s inhibition of endochondral ossification, delaying cartilage development and promoting osteoclast differentiation. Multi-omics integration identified Aspn and Sp7 as key targets in bone remodeling and resorption balance.ConclusionsMetrnl may serve as an additional diagnostic biomarker for AS and as an indicator for monitoring AS disease activity. Besides, Metrnl plays a critical role in regulating cartilage and bone metabolism and maintaining bone homeostasis, providing new insights for the future diagnosis and treatment of bone-related diseases. |
| format | Article |
| id | doaj-art-269b57c24bb545b28f0e7afa1627a8e1 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-269b57c24bb545b28f0e7afa1627a8e12025-08-20T03:14:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15951811595181Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysisZhuoqi Li0Zhuoqi Li1Tao Sun2Min Zhao3Liping Xia4Hui Shen5Department of Rheumatology and Immunology, The First Hospital of China Medical University, China Medical University, Shenyang, ChinaNational Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Rheumatology and Immunology, The First Hospital of China Medical University, China Medical University, Shenyang, ChinaNational Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Rheumatology and Immunology, The First Hospital of China Medical University, China Medical University, Shenyang, ChinaDepartment of Rheumatology and Immunology, The First Hospital of China Medical University, China Medical University, Shenyang, ChinaBackgroundAnkylosing spondylitis (AS) is an autoimmune disease characterized by bone destruction and abnormal remodeling. Metrnl, a secreted protein involved in inflammation and immune regulation, has recently been linked to bone growth. This study aimed to evaluate serum Metrnl levels in AS patients and explore its bone regulatory mechanisms using cell models and multi-omics analyses.MethodsA total of 275 participants aged 16–60 years were included to measure serum Metrnl levels using Enzyme-Linked-Immunosorbent Assay (ELISA). Correlation and receiver operating characteristic (ROC) curve analyses assessed the diagnostic and predictive value of Metrnl. Mouse pre-osteoblastic MC3T3-E1 cells were treated with recombinant Metrnl (0/10/50 ng/mL) during 28-day osteogenic differentiation. RT-qPCR and alkaline phosphatase (ALP)/Alizarin Red S (ARS) staining was used to evaluate direct osteogenic differentiation effects. Transcriptomic and proteomic studies were conducted to further explore bone metabolism mechanisms. Finally, multi-omics integration analyses identified key pathways and targets.ResultsElevated serum Metrnl levels correlated directly with disease activity markers (CRP, ESR, IL-6) in AS-Active patients, but not in AS-Stable patients. ROC analysis validated Metrnl as a potential auxiliary diagnostic biomarker for high disease activity. In vitro, Metrnl suppressed ALP/OCN expression without altering overall osteogenic differentiation. Transcriptomic and proteomic analyses revealed Metrnl’s regulatory effects on osteogenic genes and proteins, emphasizing its role in bone and cartilage development. Bioinformatics highlighted Metrnl’s inhibition of endochondral ossification, delaying cartilage development and promoting osteoclast differentiation. Multi-omics integration identified Aspn and Sp7 as key targets in bone remodeling and resorption balance.ConclusionsMetrnl may serve as an additional diagnostic biomarker for AS and as an indicator for monitoring AS disease activity. Besides, Metrnl plays a critical role in regulating cartilage and bone metabolism and maintaining bone homeostasis, providing new insights for the future diagnosis and treatment of bone-related diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595181/fullMetrnlautoimmune diseasebiomarkermulti-omicsbone metabolism |
| spellingShingle | Zhuoqi Li Zhuoqi Li Tao Sun Min Zhao Liping Xia Hui Shen Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis Frontiers in Immunology Metrnl autoimmune disease biomarker multi-omics bone metabolism |
| title | Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis |
| title_full | Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis |
| title_fullStr | Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis |
| title_full_unstemmed | Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis |
| title_short | Metrnl/Meteorin-like/IL-41, a novel regulator of bone metabolism and disease activity in ankylosing spondylitis: based on multi-omics analysis |
| title_sort | metrnl meteorin like il 41 a novel regulator of bone metabolism and disease activity in ankylosing spondylitis based on multi omics analysis |
| topic | Metrnl autoimmune disease biomarker multi-omics bone metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1595181/full |
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