Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets
Intervertebral disc degeneration (IVDD), a leading cause of chronic low back pain, imposes a significant global health burden due to its association with aging, inflammation, and mechanical stress. Emerging evidence highlights programmed cell death (PCD) as a pivotal driver of IVDD progression. PANo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1611936/full |
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| author | Kaisheng Zhou Kaisheng Zhou Mingyang Zou Mingyang Zou Shaobo Wu Shaobo Wu Wei Song Wei Song Hao Dong Hao Dong Yanbo Dong Yanbo Dong Haihong Zhang |
| author_facet | Kaisheng Zhou Kaisheng Zhou Mingyang Zou Mingyang Zou Shaobo Wu Shaobo Wu Wei Song Wei Song Hao Dong Hao Dong Yanbo Dong Yanbo Dong Haihong Zhang |
| author_sort | Kaisheng Zhou |
| collection | DOAJ |
| description | Intervertebral disc degeneration (IVDD), a leading cause of chronic low back pain, imposes a significant global health burden due to its association with aging, inflammation, and mechanical stress. Emerging evidence highlights programmed cell death (PCD) as a pivotal driver of IVDD progression. PANoptosis, a novel integrated cell death mechanism combining pyroptosis, apoptosis, and necroptosis, has recently gained attention for its role in amplifying inflammatory responses and accelerating disc degeneration. This review synthesizes current knowledge on PANoptosis in nucleus pulposus cells (NPCs), emphasizing its regulatory crosstalk via multiprotein complexes and signaling pathways such as RIPK, caspase activation, and gasdermin-mediated membrane permeabilization. Key triggers, including oxidative stress, cytokine dysregulation, and mechanical compression, exacerbate PANoptosis, leading to NPC loss and extracellular matrix degradation. While therapeutic strategies targeting PANoptosis-related molecules show promise in preclinical studies, clinical translation remains limited. Elucidating the interplay between PANoptosis and other pathological pathways could unveil novel biomarkers and therapeutic targets. This review underscores PANoptosis as a critical axis in IVDD pathogenesis and advocates for multidisciplinary approaches to bridge mechanistic insights into effective clinical interventions. |
| format | Article |
| id | doaj-art-db301c7f7be54f8e803bb3570c714d10 |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-db301c7f7be54f8e803bb3570c714d102025-08-20T03:22:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.16119361611936Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targetsKaisheng Zhou0Kaisheng Zhou1Mingyang Zou2Mingyang Zou3Shaobo Wu4Shaobo Wu5Wei Song6Wei Song7Hao Dong8Hao Dong9Yanbo Dong10Yanbo Dong11Haihong Zhang12Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaOrthopaedics Key Laboratory of Gansu Province, Lanzhou, ChinaDepartment of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, ChinaIntervertebral disc degeneration (IVDD), a leading cause of chronic low back pain, imposes a significant global health burden due to its association with aging, inflammation, and mechanical stress. Emerging evidence highlights programmed cell death (PCD) as a pivotal driver of IVDD progression. PANoptosis, a novel integrated cell death mechanism combining pyroptosis, apoptosis, and necroptosis, has recently gained attention for its role in amplifying inflammatory responses and accelerating disc degeneration. This review synthesizes current knowledge on PANoptosis in nucleus pulposus cells (NPCs), emphasizing its regulatory crosstalk via multiprotein complexes and signaling pathways such as RIPK, caspase activation, and gasdermin-mediated membrane permeabilization. Key triggers, including oxidative stress, cytokine dysregulation, and mechanical compression, exacerbate PANoptosis, leading to NPC loss and extracellular matrix degradation. While therapeutic strategies targeting PANoptosis-related molecules show promise in preclinical studies, clinical translation remains limited. Elucidating the interplay between PANoptosis and other pathological pathways could unveil novel biomarkers and therapeutic targets. This review underscores PANoptosis as a critical axis in IVDD pathogenesis and advocates for multidisciplinary approaches to bridge mechanistic insights into effective clinical interventions.https://www.frontiersin.org/articles/10.3389/fcell.2025.1611936/fullPANoptosisprogrammed cell deathnucleus pulposus cellintervertebral disc degenerationmechanism |
| spellingShingle | Kaisheng Zhou Kaisheng Zhou Mingyang Zou Mingyang Zou Shaobo Wu Shaobo Wu Wei Song Wei Song Hao Dong Hao Dong Yanbo Dong Yanbo Dong Haihong Zhang Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets Frontiers in Cell and Developmental Biology PANoptosis programmed cell death nucleus pulposus cell intervertebral disc degeneration mechanism |
| title | Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets |
| title_full | Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets |
| title_fullStr | Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets |
| title_full_unstemmed | Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets |
| title_short | Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets |
| title_sort | exploring the critical role of panoptosis in the pathogenesis of intervertebral disc degeneration mechanisms and potential therapeutic targets |
| topic | PANoptosis programmed cell death nucleus pulposus cell intervertebral disc degeneration mechanism |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1611936/full |
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