Targeting Piezo1 channel to alleviate intervertebral disc degeneration
Background: Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in the pathology and potential treatment of disc degeneration. Materials and methods:...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | Journal of Orthopaedic Translation |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214031X25000075 |
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| author | Feiyun Li Mingjue Chen Mengrui Zhang Sheng Chen Minghao Qu Shuangshuang He Lin Wang Xiaohao Wu Guozhi Xiao |
| author_facet | Feiyun Li Mingjue Chen Mengrui Zhang Sheng Chen Minghao Qu Shuangshuang He Lin Wang Xiaohao Wu Guozhi Xiao |
| author_sort | Feiyun Li |
| collection | DOAJ |
| description | Background: Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in the pathology and potential treatment of disc degeneration. Materials and methods: To investigate the effects of disc-specific Piezo1 deletion, we generated AggrecanCreERT2; Piezo1fl/fl mice and examined both lumbar spine instability (LSI)- and aging-induced disc degeneration. Additionally, the effect of pharmacological inhibition of Piezo1 was evaluated using GsMTx4, a potent Piezo1 antagonist, in an ex vivo model stimulated with IL-1β to induce disc degeneration. Assessments included histological examinations, immunofluorescence, and western blot analyses to thoroughly characterize the alterations in the intervertebral discs. Results: Elevated expression of Piezo1 was detected in the nucleus pulposus (NP) of intervertebral discs with advanced disc degeneration in both aged mice and human patients. Inducible deletion of Piezo1 expression in aggrecan-expressing disc cells significantly reduced lumbar disc degeneration, decreased extracellular matrix (ECM) degradation, and lowered apoptosis in NP cells, observed in both aged mice and those undergoing LSI surgery. Excessive compression loading (CL) upregulated Piezo1 expression, induced ECM disruption, and increased apoptosis in NP cells, whereas inhibition of Piezo1 with GsMTx4 effectively mitigated these pathological changes. Furthermore, in ex vivo cultured mouse discs, GsMTx4 treatment significantly alleviated IL-1β-induced degenerative damages, restored ECM anabolism, and reduced apoptosis. Conclusions: The findings suggest that Piezo1 plays a critical role in the development of disc degeneration and highlight its potential as a therapeutic target. Inhibiting Piezo1 could offer a novel strategy for treating or preventing this critical disease. Translational potential of this article: This research highlights the involvement of Piezo1 in the development of intervertebral disc degeneration and emphasizes the potential for targeting Piezo1 as a therapeutic strategy to delay or reverse this condition. |
| format | Article |
| id | doaj-art-aa708d51446d457f8d2be7fa88a6d493 |
| institution | Kabale University |
| issn | 2214-031X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Orthopaedic Translation |
| spelling | doaj-art-aa708d51446d457f8d2be7fa88a6d4932025-08-20T03:45:28ZengElsevierJournal of Orthopaedic Translation2214-031X2025-03-015114515810.1016/j.jot.2025.01.006Targeting Piezo1 channel to alleviate intervertebral disc degenerationFeiyun Li0Mingjue Chen1Mengrui Zhang2Sheng Chen3Minghao Qu4Shuangshuang He5Lin Wang6Xiaohao Wu7Guozhi Xiao8Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen, 518055, ChinaDepartment of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen, 518055, ChinaQuantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, CA, USADepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaSchool of Medicine, Southern University of Science and Technology, Shenzhen, China; Southern University of Science and Technology Hospital, Shenzhen, ChinaDepartment of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen, 518055, ChinaSchool of Medicine, Southern University of Science and Technology, Shenzhen, China; Southern University of Science and Technology Hospital, Shenzhen, ChinaDivision of Immunology and Rheumatology, Stanford University, Stanford, CA, 94305, USA; VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Corresponding author. Division of Immunology and Rheumatology, Stanford University, Stanford, CA, 94305, USA.Department of Biochemistry, School of Medicine, Shenzhen Key Laboratory of Cell Microenvironment, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and Technology, Shenzhen, 518055, China; Corresponding author.Background: Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in the pathology and potential treatment of disc degeneration. Materials and methods: To investigate the effects of disc-specific Piezo1 deletion, we generated AggrecanCreERT2; Piezo1fl/fl mice and examined both lumbar spine instability (LSI)- and aging-induced disc degeneration. Additionally, the effect of pharmacological inhibition of Piezo1 was evaluated using GsMTx4, a potent Piezo1 antagonist, in an ex vivo model stimulated with IL-1β to induce disc degeneration. Assessments included histological examinations, immunofluorescence, and western blot analyses to thoroughly characterize the alterations in the intervertebral discs. Results: Elevated expression of Piezo1 was detected in the nucleus pulposus (NP) of intervertebral discs with advanced disc degeneration in both aged mice and human patients. Inducible deletion of Piezo1 expression in aggrecan-expressing disc cells significantly reduced lumbar disc degeneration, decreased extracellular matrix (ECM) degradation, and lowered apoptosis in NP cells, observed in both aged mice and those undergoing LSI surgery. Excessive compression loading (CL) upregulated Piezo1 expression, induced ECM disruption, and increased apoptosis in NP cells, whereas inhibition of Piezo1 with GsMTx4 effectively mitigated these pathological changes. Furthermore, in ex vivo cultured mouse discs, GsMTx4 treatment significantly alleviated IL-1β-induced degenerative damages, restored ECM anabolism, and reduced apoptosis. Conclusions: The findings suggest that Piezo1 plays a critical role in the development of disc degeneration and highlight its potential as a therapeutic target. Inhibiting Piezo1 could offer a novel strategy for treating or preventing this critical disease. Translational potential of this article: This research highlights the involvement of Piezo1 in the development of intervertebral disc degeneration and emphasizes the potential for targeting Piezo1 as a therapeutic strategy to delay or reverse this condition.http://www.sciencedirect.com/science/article/pii/S2214031X25000075Piezo1Intervertebral disc degenerationLumbar spine instabilityAgingGsMTx4 |
| spellingShingle | Feiyun Li Mingjue Chen Mengrui Zhang Sheng Chen Minghao Qu Shuangshuang He Lin Wang Xiaohao Wu Guozhi Xiao Targeting Piezo1 channel to alleviate intervertebral disc degeneration Journal of Orthopaedic Translation Piezo1 Intervertebral disc degeneration Lumbar spine instability Aging GsMTx4 |
| title | Targeting Piezo1 channel to alleviate intervertebral disc degeneration |
| title_full | Targeting Piezo1 channel to alleviate intervertebral disc degeneration |
| title_fullStr | Targeting Piezo1 channel to alleviate intervertebral disc degeneration |
| title_full_unstemmed | Targeting Piezo1 channel to alleviate intervertebral disc degeneration |
| title_short | Targeting Piezo1 channel to alleviate intervertebral disc degeneration |
| title_sort | targeting piezo1 channel to alleviate intervertebral disc degeneration |
| topic | Piezo1 Intervertebral disc degeneration Lumbar spine instability Aging GsMTx4 |
| url | http://www.sciencedirect.com/science/article/pii/S2214031X25000075 |
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