Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages
Abstract Background Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regu...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-05-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04173-9 |
| _version_ | 1797817821045981184 |
|---|---|
| author | Yuheng Lu Hongbo Zhang Haoyan Pan Zhicheng Zhang Hua Zeng Haoyu Xie Jianbin Yin Wen Tang Rengui Lin Chun Zeng Daozhang Cai |
| author_facet | Yuheng Lu Hongbo Zhang Haoyan Pan Zhicheng Zhang Hua Zeng Haoyu Xie Jianbin Yin Wen Tang Rengui Lin Chun Zeng Daozhang Cai |
| author_sort | Yuheng Lu |
| collection | DOAJ |
| description | Abstract Background Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regulators in OA synovial cell clusters and identify key m6A regulators that mediate synovial macrophage phenotypes. Methods The expression patterns of m6A regulators in the OA synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an OA LASSO-Cox regression prediction model to identify the core m6A regulators. Potential target genes of these m6A regulators were identified by analyzing data from the RM2target database. A molecular functional network based on core m6A regulators and their target genes was constructed using the STRING database. Single-cell RNA-seq data were collected to verify the effects of m6A regulators on synovial cell clusters. Conjoint analyses of bulk and single-cell RNA-seq data were performed to validate the correlation between m6A regulators, synovial clusters, and disease conditions. After IGF2BP3 was screened as a potential modulator in OA macrophages, the IGF2BP3 expression level was tested in OA synovium and macrophages, and its functions were further tested by overexpression and knockdown in vitro. Results OA synovium showed aberrant expression patterns of m6A regulators. Based on these regulators, we constructed a well-fitting OA prediction model comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, and HNRNPC). The functional network indicated that these factors were closely associated with OA synovial phenotypic alterations. Among these regulators, the m6A reader IGF2BP3 was identified as a potential macrophage mediator. Finally, IGF2BP3 upregulation was verified in the OA synovium, which promoted macrophage M1 polarization and inflammation. Conclusions Our findings revealed the functions of m6A regulators in OA synovium and highlighted the association between IGF2BP3 and enhanced M1 polarization and inflammation in OA macrophages, providing novel molecular targets for OA diagnosis and treatment. |
| first_indexed | 2024-03-13T08:59:04Z |
| format | Article |
| id | doaj.art-136f3d3217fa4443b9f44dfd8cd3e98f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T08:59:04Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-136f3d3217fa4443b9f44dfd8cd3e98f2023-05-28T11:26:20ZengBMCJournal of Translational Medicine1479-58762023-05-0121112310.1186/s12967-023-04173-9Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophagesYuheng Lu0Hongbo Zhang1Haoyan Pan2Zhicheng Zhang3Hua Zeng4Haoyu Xie5Jianbin Yin6Wen Tang7Rengui Lin8Chun Zeng9Daozhang Cai10Department of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Orthopedics, Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical UniversityAbstract Background Disruption of N6 methyl adenosine (m6A) modulation hampers gene expression and cellular functions, leading to various illnesses. However, the role of m6A modification in osteoarthritis (OA) synovitis remains unclear. This study aimed to explore the expression patterns of m6A regulators in OA synovial cell clusters and identify key m6A regulators that mediate synovial macrophage phenotypes. Methods The expression patterns of m6A regulators in the OA synovium were illustrated by analyzing bulk RNA-seq data. Next, we built an OA LASSO-Cox regression prediction model to identify the core m6A regulators. Potential target genes of these m6A regulators were identified by analyzing data from the RM2target database. A molecular functional network based on core m6A regulators and their target genes was constructed using the STRING database. Single-cell RNA-seq data were collected to verify the effects of m6A regulators on synovial cell clusters. Conjoint analyses of bulk and single-cell RNA-seq data were performed to validate the correlation between m6A regulators, synovial clusters, and disease conditions. After IGF2BP3 was screened as a potential modulator in OA macrophages, the IGF2BP3 expression level was tested in OA synovium and macrophages, and its functions were further tested by overexpression and knockdown in vitro. Results OA synovium showed aberrant expression patterns of m6A regulators. Based on these regulators, we constructed a well-fitting OA prediction model comprising six factors (FTO, YTHDC1, METTL5, IGF2BP3, ZC3H13, and HNRNPC). The functional network indicated that these factors were closely associated with OA synovial phenotypic alterations. Among these regulators, the m6A reader IGF2BP3 was identified as a potential macrophage mediator. Finally, IGF2BP3 upregulation was verified in the OA synovium, which promoted macrophage M1 polarization and inflammation. Conclusions Our findings revealed the functions of m6A regulators in OA synovium and highlighted the association between IGF2BP3 and enhanced M1 polarization and inflammation in OA macrophages, providing novel molecular targets for OA diagnosis and treatment.https://doi.org/10.1186/s12967-023-04173-9m6A regulatorsIGF2BP3OsteoarthritisSynovial macrophages |
| spellingShingle | Yuheng Lu Hongbo Zhang Haoyan Pan Zhicheng Zhang Hua Zeng Haoyu Xie Jianbin Yin Wen Tang Rengui Lin Chun Zeng Daozhang Cai Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages Journal of Translational Medicine m6A regulators IGF2BP3 Osteoarthritis Synovial macrophages |
| title | Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages |
| title_full | Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages |
| title_fullStr | Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages |
| title_full_unstemmed | Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages |
| title_short | Expression pattern analysis of m6A regulators reveals IGF2BP3 as a key modulator in osteoarthritis synovial macrophages |
| title_sort | expression pattern analysis of m6a regulators reveals igf2bp3 as a key modulator in osteoarthritis synovial macrophages |
| topic | m6A regulators IGF2BP3 Osteoarthritis Synovial macrophages |
| url | https://doi.org/10.1186/s12967-023-04173-9 |
| work_keys_str_mv | AT yuhenglu expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT hongbozhang expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT haoyanpan expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT zhichengzhang expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT huazeng expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT haoyuxie expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT jianbinyin expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT wentang expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT renguilin expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT chunzeng expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages AT daozhangcai expressionpatternanalysisofm6aregulatorsrevealsigf2bp3asakeymodulatorinosteoarthritissynovialmacrophages |