Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets
Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods T...
Ausführliche Beschreibung
Autor*in: |
Jin, Zhuangzhuang [verfasserIn] |
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E-Artikel |
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Englisch |
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2023 |
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Anmerkung: |
© The Author(s) 2023 |
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Übergeordnetes Werk: |
Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 21(2023), 1 vom: 23. Sept. |
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Übergeordnetes Werk: |
volume:21 ; year:2023 ; number:1 ; day:23 ; month:09 |
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DOI / URN: |
10.1186/s12967-023-04541-5 |
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Katalog-ID: |
SPR053176340 |
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520 | |a Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. | ||
650 | 4 | |a Bioinformatics analysis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Iron overload |7 (dpeaa)DE-He213 | |
650 | 4 | |a Osteoarthritis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Single-cell RNA-seq analysis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Synovium |7 (dpeaa)DE-He213 | |
650 | 4 | |a Validation experiments |7 (dpeaa)DE-He213 | |
700 | 1 | |a Zhang, He |4 aut | |
700 | 1 | |a Bai, Lunhao |4 aut | |
700 | 1 | |a Yue, Lingyu |4 aut | |
700 | 1 | |a Zhang, Weiming |4 aut | |
700 | 1 | |a Liang, Jiajian |4 aut | |
700 | 1 | |a Chang, Bohan |4 aut | |
700 | 1 | |a Yang, Yue |4 aut | |
700 | 1 | |a Hu, Zhehan |4 aut | |
700 | 1 | |a Chen, Liang |4 aut | |
700 | 1 | |a Guo, Chuanji |4 aut | |
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10.1186/s12967-023-04541-5 doi (DE-627)SPR053176340 (SPR)s12967-023-04541-5-e DE-627 ger DE-627 rakwb eng Jin, Zhuangzhuang verfasserin aut Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. Bioinformatics analysis (dpeaa)DE-He213 Iron overload (dpeaa)DE-He213 Osteoarthritis (dpeaa)DE-He213 Single-cell RNA-seq analysis (dpeaa)DE-He213 Synovium (dpeaa)DE-He213 Validation experiments (dpeaa)DE-He213 Zhang, He aut Bai, Lunhao aut Yue, Lingyu aut Zhang, Weiming aut Liang, Jiajian aut Chang, Bohan aut Yang, Yue aut Hu, Zhehan aut Chen, Liang aut Guo, Chuanji aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 23. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:23 month:09 https://dx.doi.org/10.1186/s12967-023-04541-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 23 09 |
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10.1186/s12967-023-04541-5 doi (DE-627)SPR053176340 (SPR)s12967-023-04541-5-e DE-627 ger DE-627 rakwb eng Jin, Zhuangzhuang verfasserin aut Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. Bioinformatics analysis (dpeaa)DE-He213 Iron overload (dpeaa)DE-He213 Osteoarthritis (dpeaa)DE-He213 Single-cell RNA-seq analysis (dpeaa)DE-He213 Synovium (dpeaa)DE-He213 Validation experiments (dpeaa)DE-He213 Zhang, He aut Bai, Lunhao aut Yue, Lingyu aut Zhang, Weiming aut Liang, Jiajian aut Chang, Bohan aut Yang, Yue aut Hu, Zhehan aut Chen, Liang aut Guo, Chuanji aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 23. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:23 month:09 https://dx.doi.org/10.1186/s12967-023-04541-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 23 09 |
allfields_unstemmed |
10.1186/s12967-023-04541-5 doi (DE-627)SPR053176340 (SPR)s12967-023-04541-5-e DE-627 ger DE-627 rakwb eng Jin, Zhuangzhuang verfasserin aut Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. Bioinformatics analysis (dpeaa)DE-He213 Iron overload (dpeaa)DE-He213 Osteoarthritis (dpeaa)DE-He213 Single-cell RNA-seq analysis (dpeaa)DE-He213 Synovium (dpeaa)DE-He213 Validation experiments (dpeaa)DE-He213 Zhang, He aut Bai, Lunhao aut Yue, Lingyu aut Zhang, Weiming aut Liang, Jiajian aut Chang, Bohan aut Yang, Yue aut Hu, Zhehan aut Chen, Liang aut Guo, Chuanji aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 23. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:23 month:09 https://dx.doi.org/10.1186/s12967-023-04541-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 23 09 |
allfieldsGer |
10.1186/s12967-023-04541-5 doi (DE-627)SPR053176340 (SPR)s12967-023-04541-5-e DE-627 ger DE-627 rakwb eng Jin, Zhuangzhuang verfasserin aut Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. Bioinformatics analysis (dpeaa)DE-He213 Iron overload (dpeaa)DE-He213 Osteoarthritis (dpeaa)DE-He213 Single-cell RNA-seq analysis (dpeaa)DE-He213 Synovium (dpeaa)DE-He213 Validation experiments (dpeaa)DE-He213 Zhang, He aut Bai, Lunhao aut Yue, Lingyu aut Zhang, Weiming aut Liang, Jiajian aut Chang, Bohan aut Yang, Yue aut Hu, Zhehan aut Chen, Liang aut Guo, Chuanji aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 23. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:23 month:09 https://dx.doi.org/10.1186/s12967-023-04541-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 23 09 |
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10.1186/s12967-023-04541-5 doi (DE-627)SPR053176340 (SPR)s12967-023-04541-5-e DE-627 ger DE-627 rakwb eng Jin, Zhuangzhuang verfasserin aut Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. Bioinformatics analysis (dpeaa)DE-He213 Iron overload (dpeaa)DE-He213 Osteoarthritis (dpeaa)DE-He213 Single-cell RNA-seq analysis (dpeaa)DE-He213 Synovium (dpeaa)DE-He213 Validation experiments (dpeaa)DE-He213 Zhang, He aut Bai, Lunhao aut Yue, Lingyu aut Zhang, Weiming aut Liang, Jiajian aut Chang, Bohan aut Yang, Yue aut Hu, Zhehan aut Chen, Liang aut Guo, Chuanji aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 21(2023), 1 vom: 23. Sept. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:21 year:2023 number:1 day:23 month:09 https://dx.doi.org/10.1186/s12967-023-04541-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2023 1 23 09 |
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Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets |
abstract |
Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. © The Author(s) 2023 |
abstractGer |
Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. © The Author(s) 2023 |
abstract_unstemmed |
Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and $ Fe^{2+} $ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis. © The Author(s) 2023 |
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title_short |
Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets |
url |
https://dx.doi.org/10.1186/s12967-023-04541-5 |
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author2 |
Zhang, He Bai, Lunhao Yue, Lingyu Zhang, Weiming Liang, Jiajian Chang, Bohan Yang, Yue Hu, Zhehan Chen, Liang Guo, Chuanji |
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Zhang, He Bai, Lunhao Yue, Lingyu Zhang, Weiming Liang, Jiajian Chang, Bohan Yang, Yue Hu, Zhehan Chen, Liang Guo, Chuanji |
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doi_str |
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up_date |
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The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and $ Fe^{2+} $ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. 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