Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration
Abstract Background Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used to diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s13075-025-03489-9 |
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| author | Christabel Thembela Dube Hamish T. J. Gilbert Niamh Rabbitte Pauline Baird Sonal Patel Jeremy A. Herrera Ivona Baricevic-Jones Richard D. Unwin Danny Chan Kanna Gnanalingham Judith A. Hoyland Stephen M. Richardson |
| author_facet | Christabel Thembela Dube Hamish T. J. Gilbert Niamh Rabbitte Pauline Baird Sonal Patel Jeremy A. Herrera Ivona Baricevic-Jones Richard D. Unwin Danny Chan Kanna Gnanalingham Judith A. Hoyland Stephen M. Richardson |
| author_sort | Christabel Thembela Dube |
| collection | DOAJ |
| description | Abstract Background Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used to diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in the tissue extracellular matrix (ECM) as degeneration progresses. Improved techniques, such as a combination of tissue and blood biomarkers, are needed to monitor the progression of IVD degeneration for more effective treatment plans. Methods To identify tissue and blood biomarkers associated with degeneration progression, we histologically graded 35 adult human degenerate IVD tissues and matched plasma from the individuals into two groups: mild degenerate and severe degenerate. Mass spectrometry was utilised to characterise proteomic differences in tissue and plasma between the two groups. Top differentially distributed proteins were further validated using immunohistochemistry and qRT-PCR. Additionally, correlational analyses were conducted to define similarities and differences between tissue and plasma protein changes in individuals with mild and severe IVD degeneration. Results Our data revealed that the abundance of 31 proteins was significantly increased in severe degenerated IVD tissues compared to mild. Functional analyses showed that more than 40% of these proteins were matrisome-related, indicating differences in ECM protein composition between severe and mild degenerate IVD tissues. We confirmed adipocyte enhancer-binding protein 1 (AEBP1) as one of the most significantly enriched core matrisome genes and proteins as degeneration progressed. Compared to others, AEBP1 protein levels best distinguished between mild and severe degenerated IVD tissues with an area under the curve score of 0.768 (95% CI: 0.60–0.93). However, we found that protein changes from associated plasma exhibited a weak relationship with histological grading and AEBP1 tissue levels. Given that systemic plasma changes are complex, a larger sample cohort may be required to identify patterns in blood relating to IVD degeneration progression. Conclusions In this study, we have identified AEBP1 as a tissue marker for monitoring the severity of disc degeneration in humans. Further work to link alterations in tissue AEBP1 levels to changes in blood-related proteins will be beneficial for detailed monitoring of IVD degeneration thereby enabling more personalised treatment approaches. |
| format | Article |
| id | doaj-art-387ec248f1fa40a8a63e6645a2aeaf72 |
| institution | DOAJ |
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| language | English |
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| spelling | doaj-art-387ec248f1fa40a8a63e6645a2aeaf722025-08-20T02:43:13ZengBMCArthritis Research & Therapy1478-63622025-02-0127111810.1186/s13075-025-03489-9Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degenerationChristabel Thembela Dube0Hamish T. J. Gilbert1Niamh Rabbitte2Pauline Baird3Sonal Patel4Jeremy A. Herrera5Ivona Baricevic-Jones6Richard D. Unwin7Danny Chan8Kanna Gnanalingham9Judith A. Hoyland10Stephen M. Richardson11Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterManchester Cell-Matrix Centre, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterStoller Biomarker Discovery Centre, Faculty of Biology, Medicine and Health, The University of ManchesterStoller Biomarker Discovery Centre, Faculty of Biology, Medicine and Health, The University of ManchesterSchool of Biomedical Sciences, Faculty of Medicine Building, The University of Hong KongDepartment of Neurosurgery, Manchester Academy of Health Science Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation TrustDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterDivision of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of ManchesterAbstract Background Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used to diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in the tissue extracellular matrix (ECM) as degeneration progresses. Improved techniques, such as a combination of tissue and blood biomarkers, are needed to monitor the progression of IVD degeneration for more effective treatment plans. Methods To identify tissue and blood biomarkers associated with degeneration progression, we histologically graded 35 adult human degenerate IVD tissues and matched plasma from the individuals into two groups: mild degenerate and severe degenerate. Mass spectrometry was utilised to characterise proteomic differences in tissue and plasma between the two groups. Top differentially distributed proteins were further validated using immunohistochemistry and qRT-PCR. Additionally, correlational analyses were conducted to define similarities and differences between tissue and plasma protein changes in individuals with mild and severe IVD degeneration. Results Our data revealed that the abundance of 31 proteins was significantly increased in severe degenerated IVD tissues compared to mild. Functional analyses showed that more than 40% of these proteins were matrisome-related, indicating differences in ECM protein composition between severe and mild degenerate IVD tissues. We confirmed adipocyte enhancer-binding protein 1 (AEBP1) as one of the most significantly enriched core matrisome genes and proteins as degeneration progressed. Compared to others, AEBP1 protein levels best distinguished between mild and severe degenerated IVD tissues with an area under the curve score of 0.768 (95% CI: 0.60–0.93). However, we found that protein changes from associated plasma exhibited a weak relationship with histological grading and AEBP1 tissue levels. Given that systemic plasma changes are complex, a larger sample cohort may be required to identify patterns in blood relating to IVD degeneration progression. Conclusions In this study, we have identified AEBP1 as a tissue marker for monitoring the severity of disc degeneration in humans. Further work to link alterations in tissue AEBP1 levels to changes in blood-related proteins will be beneficial for detailed monitoring of IVD degeneration thereby enabling more personalised treatment approaches.https://doi.org/10.1186/s13075-025-03489-9Intervertebral discDegenerationHistological gradingExtracellular matrixProteomicsBiomarkers |
| spellingShingle | Christabel Thembela Dube Hamish T. J. Gilbert Niamh Rabbitte Pauline Baird Sonal Patel Jeremy A. Herrera Ivona Baricevic-Jones Richard D. Unwin Danny Chan Kanna Gnanalingham Judith A. Hoyland Stephen M. Richardson Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration Arthritis Research & Therapy Intervertebral disc Degeneration Histological grading Extracellular matrix Proteomics Biomarkers |
| title | Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration |
| title_full | Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration |
| title_fullStr | Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration |
| title_full_unstemmed | Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration |
| title_short | Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration |
| title_sort | proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal but not plasma biomarkers of disc degeneration |
| topic | Intervertebral disc Degeneration Histological grading Extracellular matrix Proteomics Biomarkers |
| url | https://doi.org/10.1186/s13075-025-03489-9 |
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