E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc
Abstract Background Intervertebral disc degeneration (IVDD) is one of the main causes of chronic low back pain. The degenerative process is often initiated by an imbalance between catabolic and anabolic pathways. Despite the large socio‐economic impact, the initiation and progress of disc degenerati...
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Wiley
2025-03-01
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| Online Access: | https://doi.org/10.1002/jsp2.70016 |
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| author | María González‐Rodríguez Djedjiga Ait Eldjoudi Alfonso Cordero‐Barreal Mariam Farrag María Varela‐García Clara Ruiz‐Fernández Carlos Torrijos‐Pulpón Francisca Lago Lucía García‐Caballero Yousof Farrag Javier Conde‐Aranda Jesus Pino Oreste Gualillo |
| author_facet | María González‐Rodríguez Djedjiga Ait Eldjoudi Alfonso Cordero‐Barreal Mariam Farrag María Varela‐García Clara Ruiz‐Fernández Carlos Torrijos‐Pulpón Francisca Lago Lucía García‐Caballero Yousof Farrag Javier Conde‐Aranda Jesus Pino Oreste Gualillo |
| author_sort | María González‐Rodríguez |
| collection | DOAJ |
| description | Abstract Background Intervertebral disc degeneration (IVDD) is one of the main causes of chronic low back pain. The degenerative process is often initiated by an imbalance between catabolic and anabolic pathways. Despite the large socio‐economic impact, the initiation and progress of disc degeneration are poorly understood. Although intervertebral disc (IVD) and articular joint are not identical, their degenerative roads are remarkably similar. We, and another authors, previously demonstrated that E‐74‐like factor 3 (ELF3), a transcription factor induced by inflammatory mediators in various cell types including chondrocytes, is a central contributing factor for cartilage degradation. Thus, we aim to explore, for the first time, the expression, modulation, and the role of ELF3 in human IVD cells. Methods The presence of ELF3 in healthy and degenerated IVD tissues was initially determined by immunohistochemistry in annulus fibrosus (AF) and nucleus pulposus (NP). mRNA and protein expression were measured, respectively, by RT‐qPCR and Western blot in AF and NP IVD cells harvested from healthy individuals and IVDD patients. Overexpression of ELF3 was performed by transfection of AF IVDD cells with pESE‐1: ELF3 expression vector or pCI: empty vector. Results Our results unveiled, for the first time, the expression of ELF3 in IVD tissues. ELF3 is notably upregulated in degenerated tissues compared to those from healthy patients. In addition, the stimulation of IVDD AF cells with various proinflammatory stimuli, showed marked increase in both mRNA and protein expression of ELF3. ELF3 overexpression in AF IVDD cells resulted in the upregulation of proinflammatory and catabolic genes such as PTGS2, NOS2, LCN2, IL‐6, MMP13, and ADAMTS‐5; whereas, ELF3 silencing resulted in the opposite results. Conclusions Our results support a novel role for ELF3 as a pro‐inflammatory and pro‐catabolic transcriptional mediator, whose targeting in IVD tissues might be of potential therapeutic relevance in disc degeneration. |
| format | Article |
| id | doaj-art-592d1a811ca74219a0a555a92654dabc |
| institution | Kabale University |
| issn | 2572-1143 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| spelling | doaj-art-592d1a811ca74219a0a555a92654dabc2025-08-20T03:48:45ZengWileyJOR Spine2572-11432025-03-0181n/an/a10.1002/jsp2.70016E74‐like ETS transcription factor 3 expression and regulation in human intervertebral discMaría González‐Rodríguez0Djedjiga Ait Eldjoudi1Alfonso Cordero‐Barreal2Mariam Farrag3María Varela‐García4Clara Ruiz‐Fernández5Carlos Torrijos‐Pulpón6Francisca Lago7Lucía García‐Caballero8Yousof Farrag9Javier Conde‐Aranda10Jesus Pino11Oreste Gualillo12SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainMolecular and Cellular Cardiology Group, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Research Laboratory 7 Santiago University Clinical Hospital Santiago de Compostela SpainDepartment of Morphological Sciences. School of Medicine and Dentistry University of Santiago de Compostela Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainMolecular and Cellular Gastroenterology Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainSERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases) Santiago University Clinical Hospital Santiago de Compostela SpainAbstract Background Intervertebral disc degeneration (IVDD) is one of the main causes of chronic low back pain. The degenerative process is often initiated by an imbalance between catabolic and anabolic pathways. Despite the large socio‐economic impact, the initiation and progress of disc degeneration are poorly understood. Although intervertebral disc (IVD) and articular joint are not identical, their degenerative roads are remarkably similar. We, and another authors, previously demonstrated that E‐74‐like factor 3 (ELF3), a transcription factor induced by inflammatory mediators in various cell types including chondrocytes, is a central contributing factor for cartilage degradation. Thus, we aim to explore, for the first time, the expression, modulation, and the role of ELF3 in human IVD cells. Methods The presence of ELF3 in healthy and degenerated IVD tissues was initially determined by immunohistochemistry in annulus fibrosus (AF) and nucleus pulposus (NP). mRNA and protein expression were measured, respectively, by RT‐qPCR and Western blot in AF and NP IVD cells harvested from healthy individuals and IVDD patients. Overexpression of ELF3 was performed by transfection of AF IVDD cells with pESE‐1: ELF3 expression vector or pCI: empty vector. Results Our results unveiled, for the first time, the expression of ELF3 in IVD tissues. ELF3 is notably upregulated in degenerated tissues compared to those from healthy patients. In addition, the stimulation of IVDD AF cells with various proinflammatory stimuli, showed marked increase in both mRNA and protein expression of ELF3. ELF3 overexpression in AF IVDD cells resulted in the upregulation of proinflammatory and catabolic genes such as PTGS2, NOS2, LCN2, IL‐6, MMP13, and ADAMTS‐5; whereas, ELF3 silencing resulted in the opposite results. Conclusions Our results support a novel role for ELF3 as a pro‐inflammatory and pro‐catabolic transcriptional mediator, whose targeting in IVD tissues might be of potential therapeutic relevance in disc degeneration.https://doi.org/10.1002/jsp2.70016catabolismE74‐like ETS transcription factor 3ETS transcription factorshuman intervertebral discinflammationIVDD |
| spellingShingle | María González‐Rodríguez Djedjiga Ait Eldjoudi Alfonso Cordero‐Barreal Mariam Farrag María Varela‐García Clara Ruiz‐Fernández Carlos Torrijos‐Pulpón Francisca Lago Lucía García‐Caballero Yousof Farrag Javier Conde‐Aranda Jesus Pino Oreste Gualillo E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc JOR Spine catabolism E74‐like ETS transcription factor 3 ETS transcription factors human intervertebral disc inflammation IVDD |
| title | E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc |
| title_full | E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc |
| title_fullStr | E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc |
| title_full_unstemmed | E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc |
| title_short | E74‐like ETS transcription factor 3 expression and regulation in human intervertebral disc |
| title_sort | e74 like ets transcription factor 3 expression and regulation in human intervertebral disc |
| topic | catabolism E74‐like ETS transcription factor 3 ETS transcription factors human intervertebral disc inflammation IVDD |
| url | https://doi.org/10.1002/jsp2.70016 |
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