Prominin-2/FBXO22/BACH1 axis protects bone marrow mesenchymal stem cells against TBHP-induced ferroptosis and ameliorates intervertebral disc degeneration.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-07-01 DOI:10.1186/s13287-025-04453-9

Yuzhu Xu, Lele Zhang, Mingliang Ji, Jun Lu

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引用次数: 0

Abstract

Background: Our preliminary research has revealed that Prominin-2 overexpression effectively guarded against oxidative stress (OS)-induced ferroptosis by decreasing BTB and CNC homolog 1 (BACH1) expression, thus promoting bone marrow mesenchymal stem cells (BMSCs) survival under the OS microenvironments in degenerative discs.

Methods: In this study, we probed how Prominin-2 controls the BACH1 expression in OS-induced BMSC ferroptosis. We then evaluated the efficiency of targeted Prominin-2/BACH1 pathway in BMSCs in treating degenerative nucleus pulposus cells (NPCs) and intervertebral disc degeneration (IVDD).

Results: Using lentivirus infection and Western Blot, we observed that F-box only protein 22 (FBXO22) levels decreased in OS-induced BMSCs while overexpressing Prominin-2 restored its expression and pharmacological inhibition of FBXO22 impaired Prominin-2-mediated BACH1 degradation. The pull-down assay further confirmed the essential role of FBXO22 in the degradation of BACH1 promoted by Prominin-2. FBXO22 overexpression suppressed BMSCs' ferroptosis, and FBXO22 activity enhancer TBE56 (biotinylated TBE31) could further improve Prominin-2-overexpressed BMSCs' viability under OS circumstances. Finally, in vitro co-culture and in vivo studies illustrated that engraftment of Prominin-2-overexpressed BMSCs pre-treated by TBE56 enhanced the treatment efficiency of BMSCs for degenerative NPCs and rats' IVDD.

Conclusions: Our data proposed a novel treatment strategy targeting the ferroptosis of BMSCs for treating IVDD by regulating FBXO22 in Prominin-2-overexpressed BMSCs.

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突出蛋白-2/FBXO22/BACH1轴保护骨髓间充质干细胞免受thbhp诱导的铁下垂和改善椎间盘退变。

背景：我们的初步研究发现，过表达的突起2通过降低BTB和CNC同源物1 （BACH1）的表达，有效地保护氧化应激（OS）诱导的铁凋亡，从而促进退变椎间盘在OS微环境下骨髓间充质干细胞（BMSCs）的存活。方法：本研究探讨了在os诱导的BMSC铁下垂中，prominent -2对BACH1表达的调控作用。然后，我们评估了骨髓间质干细胞中靶向的突起蛋白-2/BACH1通路治疗退行性髓核细胞（NPCs）和椎间盘退变（IVDD）的效率。结果：通过慢病毒感染和Western Blot，我们观察到os诱导的骨髓间充质干细胞中F-box only蛋白22 （FBXO22）水平下降，而过表达的珥蛋白-2恢复了其表达，FBXO22的药理抑制破坏了珥蛋白-2介导的BACH1降解。下拉实验进一步证实了FBXO22在由prominent -2促进的BACH1降解过程中的重要作用。FBXO22过表达可抑制骨髓间充质干细胞的铁凋亡，FBXO22活性增强剂TBE56（生物素化TBE31）可进一步提高OS条件下过表达的骨髓间充质干细胞的活力。最后，体外共培养和体内研究表明，移植经TBE56预处理的过表达的间充质干细胞可提高间充质干细胞对退行性npc和大鼠IVDD的治疗效率。结论：我们的数据提出了一种新的治疗策略，通过调节过表达的突出蛋白-2的骨髓间充质干细胞中的FBXO22来治疗IVDD。

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来源期刊

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.