时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
Despite extensive research efforts in recent years, the specific pathogenesis of IVDD remains incompletely elucidated.；Building upon these observations, we hypothesized that PHGDH downregulation and the consequent disruption of serine metabolism are critical drivers of nucleus pulposus cell senescence.
方法
The tissue samples were obtained from 8 patients diagnosed with IVDD and 8 patients with burst vertebrae but normal intervertebral discs admitted to our hospital between February 2024 and Dec 2024.；Following discectomy, the intervertebral discs were promptly fixed in 4% paraformaldehyde, followed by embedding and sectioning.；All patients and their families signed informed consent forms, and both human and animal experimentation were approved by the Medical Ethics Committee of Shanghai East Hospital (2022‐2025). 24 healthy 2‐month‐old male Sprague‐Dawley (SD) rats were housed in a room maintained at approximately 25°C with a humidity of 60%, under a 12‐h light/12‐h dark cycle. 8 male SD rats were anesthetized via intraperitoneal injection of 3% pentobarbital sodium (30 mg/kg).
核心结论
SA‐β‐gal staining confirmed a significant increase in senescence‐associated β‐galactosidase activity in both RS and SIPS models (Figure ).；Consistently, Western blot analysis revealed increased protein levels of the classic senescence markers P21 and P16 (Figure ).；These data collectively confirm that both senescence models exhibit robust and consistent senescent phenotypes. ‖ 结论：Taken together with the oxidative stress and GSH depletion induced by serine deprivation in this study, we propose that PHGDH‐mediated serine metabolism cooperatively protects NPC homeostasis through multiple pathways encompassing epigenetics, autophagy, and redox regulation.
局限
In this study, we uncover that PHGDH, the rate‐limiting enzyme of the serine synthesis pathway, acts as a metabolic sentinel that safeguards NPCs against senescence and IVDD.；PHGDH is one of the three rate‐limiting enzymes in the de novo serine synthesis pathway.；Mechanistically, serine is a major one‐carbon donor and a precursor for glycine and cysteine, the two rate‐limiting amino acids for GSH synthesis [].
对本项目的价值
★☆☆☆☆ 代谢轴既干预敏感性最高，也是老药新用供给最充足的来源。设计 single cell。
全文来源
PMC JATS 全文（正文 54,726 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：PHGDH-Mediated Serine Metabolism in Nucleus Pulposus Cells Is a Potential Therapeutic Target for Intervertebral Disc Degeneration.
- 期刊与标识：Adv Sci (Weinh) · PMID 42949656 · DOI 10.1002/advs.78581
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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