USP13 在 BMSCs 中的过表达可增强抗凋亡能力,防止甲泼尼龙诱导的大鼠骨坏死。

IF 4 2区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY STEM CELLS Pub Date : 2024-10-26 DOI:10.1093/stmcls/sxae069
Yixin Jiang, Xiaoli Fan, Yaling Yu, Hongfan Ge, Chengyin Liu, Yanyan Zhang, Lingyun Yu, Wen Yin, Zhenlei Zhou
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引用次数: 0

摘要

甲基强的松龙(MPS)的使用与股骨头坏死(ONFH)病例的增加有关。骨髓间充质干细胞(BMSCs)已显示出治疗MPS诱发的股骨头坏死的潜力,但其有效性因移植后的高凋亡率而受到限制。我们开发了一种预处理 BMSCs 的策略,以提高其存活率。在 MPS 诱导的 ONFH 大鼠模型中,我们通过显微 CT、HE 染色和 TUNEL 染色评估了 USP13 在 BMSCs 中的过表达效果。与普通 BMSCs 和直接注射慢病毒相比,过表达 USP13 的 BMSCs 能明显减轻 ONFH 的严重程度。USP13 还能通过调节 PTEN 和减少 AKT 磷酸化保护 BMSCs 免受 MPS 诱导的细胞凋亡。这导致 USP13 高表达 BMSCs 中凋亡基因和蛋白的表达减少。我们的研究结果突出表明,USP13 是提高 BMSC 存活率和治疗 MPS 诱导的 ONFH 疗效的一个有前途的靶点。
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USP13 Overexpression in BMSCs Enhances Anti-Apoptotic Ability and Guards Against Methylprednisolone-Induced Osteonecrosis in Rats.

Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pre-treatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.

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来源期刊
STEM CELLS
STEM CELLS 医学-生物工程与应用微生物
CiteScore
10.30
自引率
1.90%
发文量
104
审稿时长
3 months
期刊介绍: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.
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