{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:29:09Z","timestamp":1786512549839,"version":"build-2736575974"},"reference-count":44,"publisher":"The Korean Spinal Neurosurgery Society","issue":"3","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272536"],"award-info":[{"award-number":["82272536"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","award":["2025CXZX-117"],"award-info":[{"award-number":["2025CXZX-117"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-neurospine.org"],"crossmark-restriction":true},"short-container-title":["NS"],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:p>Objective: This study aimed to investigate the role of the STAT3\/POSTN\/GSTP1\/JNK axis in ferroptosis and extracellular matrix (ECM) metabolic imbalance in nucleus pulposus cells (NPCs) during intervertebral disc degeneration (IDD) and to explore therapeutic strategies targeting this axis.Methods: Using integrated multiomics sequencing, transcriptional regulation assays (chromatin immunoprecipitation, dual\u2011luciferase reporter), protein interaction analysis (CoIP), and other molecular biology approaches, we systematically elucidated the regulatory role of the STAT3\/POSTN\/GSTP1\/JNK axis in ferroptosis of NPCs during IDD. Functional validation was performed in POSTN\u2011edited cell and rat models as well as in a needle\u2011puncture\u2011induced rat IDD model. A small\u2011molecule candidate targeting this axis was identified through virtual screening, molecular docking, and molecular dynamics simulations.Results: Periostin (POSTN) expression increased during ferroptosis and induced ferroptosis and ECM metabolic imbalance in NPCs in a concentration- and time-dependent manner. STAT3 was identified as a transcriptional regulator of POSTN and functionally coupled with POSTN to form a self-amplifying positive feedback loop, accelerating ferroptosis progression. Furthermore, POSTN impaired the binding of the GSTP1\/JNK complex, leading to the depletion of cellular glutathione. Chemical screening identified pristimerin (PN) as a potential GSTP1-targeting compound, targeting the STAT3\/POSTN\/GSTP1\/JNK axis and delaying IDD progression.Conclusion: This study identified the important role of the STAT3\/POSTN\/GSTP1\/JNK axis in regulating ferroptosis and ECM metabolism in NPCs and highlighted PN as a promising candidate therapeutic agent for IDD. These findings provide new insights into the molecular mechanisms underlying IDD and offer new targeted therapeutic avenues for IDD.<\/jats:p>","DOI":"10.14245\/ns.26520334.0167","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:15:42Z","timestamp":1785402942000},"page":"644-664","update-policy":"https:\/\/doi.org\/10.14245\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["STAT3\/POSTN\/GSTP1\/JNK Axis Orchestrates Ferroptosis in Nucleus Pulposus Cells: A Potential Therapeutic Target for Intervertebral Disc Degeneration"],"prefix":"10.14245","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-5073","authenticated-orcid":true,"given":"Zhaoheng","family":"Wang","sequence":"first","affiliation":[{"name":"Lanzhou University Second Hospital, Lanzhou, China"},{"name":"Key Laboratory of Orthopedics Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou, 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