Modulation of Osteogenic Differentiation by CYBB in Osteoporotic Models

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2025-05-02 DOI:10.1002/iub.70023
Zhaodong Wang, Chen Xu, Yajun Liu, Keyou Duan, Zhonglian Zhu, Jianzhong Guan
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引用次数: 0

Abstract

Osteoporosis (OP) is a prevalent systemic skeletal disease characterized by increased bone fragility and fracture risk. Identifying factors that influence osteogenic differentiation in OP is crucial. We screened genes associated with OP from the Gene Expression Omnibus (GEO) database and constructed a weighted correlation network analysis (WGCNA) to identify hub genes, validating our findings in external and clinical cohorts. Various experiments assessed the proliferation, apoptosis, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs) following CYBB knockdown. We established a postmenopausal OP model in rats through bilateral ovariectomy (OVX) and evaluated OP severity using three-dimensional computed tomography (3D-CT) and H&E staining. Differential gene expression analysis revealed that CYBB was significantly upregulated in OP, with the highest area under the curve (AUC) among differentially expressed genes (DEGs). Notably, CYBB expression in BMSCs decreased over time. Knockdown of CYBB promoted BMSC proliferation and reduced apoptosis, as demonstrated by Alizarin red and ALP staining, which indicated enhanced osteogenic differentiation. Markers such as RUNX1, RUNX2, ALP, secreted phosphoprotein 1 (SPP1), and bone sialoprotein (BSP) were upregulated post-knockdown. In vivo, CYBB knockdown improved bone mineral density (BMD), relative bone volume fraction (BV/TV), and trabecular number (Tb.N). In conclusion, CYBB influences OP progression by modulating bone formation.

CYBB对骨质疏松模型成骨分化的调节作用
骨质疏松症(OP)是一种普遍存在的全身性骨骼疾病,其特征是骨质疏松和骨折风险增加。确定影响OP成骨分化的因素至关重要。我们从Gene Expression Omnibus (GEO)数据库中筛选与OP相关的基因,并构建加权相关网络分析(WGCNA)来确定中心基因,在外部和临床队列中验证我们的发现。各种实验评估了CYBB敲除后骨髓间充质干细胞(BMSCs)的增殖、凋亡和成骨分化能力。我们通过双侧卵巢切除术(OVX)建立大鼠绝经后OP模型,并通过三维计算机断层扫描(3D-CT)和H&;E染色评估OP严重程度。差异基因表达分析显示,CYBB在OP中显著上调,其曲线下面积(AUC)在差异表达基因(deg)中最高。值得注意的是,骨髓间充质干细胞中CYBB的表达随着时间的推移而下降。茜素红和ALP染色显示,CYBB的下调促进了BMSC的增殖,减少了细胞凋亡,表明成骨分化增强。RUNX1、RUNX2、ALP、分泌磷酸化蛋白1 (SPP1)和骨唾液蛋白(BSP)等标志物在敲除后上调。在体内,CYBB敲除可改善骨密度(BMD)、相对骨体积分数(BV/TV)和小梁数(Tb.N)。综上所述,CYBB通过调节骨形成影响OP进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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