过度表达基质细胞衍生因子 1 的骨髓间充质干细胞有助于骨质疏松小鼠的骨形成。

IF 2.2 3区 医学 Q2 ORTHOPEDICS BMC Musculoskeletal Disorders Pub Date : 2024-11-04 DOI:10.1186/s12891-024-07957-2
Yanghao Wang, Ya Xiao, XinYu Yang, Fei He, Jun Hu, Guang Yang, Weizhou Wang
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引用次数: 0

摘要

背景:骨质疏松症的特点是全身骨矿物质含量低和骨微结构破坏。通过输注外源性骨髓间充质干细胞(BMSCs)促进骨再生和逆转骨流失是治疗骨质疏松症的一种潜在有效方法。然而,间充质干细胞向靶器官的迁移有限,降低了细胞的治疗效果。基质细胞衍生因子1(SDF1)是一种趋化因子,可通过SDF1/CXCR4(C-X-C趋化因子受体4)轴诱导靶细胞迁移,并可诱导外源性间充质干细胞向SDF1浓度高的部位迁移。目前还没有关于骨质疏松小鼠体内过表达 SDF1 的 BMSCs(SDF1-BMSCs)的研究。我们的目的是研究 SDF1 浓度的增加是否促进了细胞向骨骼的迁移:方法:我们使用慢病毒构建过表达 SDF1 或敲除 CXCR4 的 BMSCs。方法:我们使用慢病毒构建了过表达 SDF1 或敲除 CXCR4 的 BMSCs,并使用细胞计数试剂盒-8(CCK8)和 5-溴脱氧尿苷(BrdU)检测了细胞的体外增殖能力,使用 Transwell 检测了细胞的迁移能力,使用成骨和成脂诱导液检测了细胞的成骨和成脂能力。在体内实验中,我们通过卵巢切除术诱导 72 只雌性小鼠患上骨质疏松症,并通过尾静脉注射不同组别的细胞。收集固定时间的股骨组织样本,通过显微CT和组织切片染色验证细胞的成骨和归巢能力:结果:我们成功地证明了高表达 SDF1 可促进体外细胞增殖和迁移,而不影响其细胞分化能力。在卵巢切除的小鼠模型中,SDF1-BMSCs比BMSCs更容易归巢到股骨,具有更好的促成骨细胞能力,Wnt-1的表达量也更高。阻断SDF1/CXCR4轴可减少外源性间充质干细胞(MSCs)向股骨的归巢及其成骨能力:结论:SDF1-BMSCs可通过增加骨质疏松小鼠股骨归巢细胞的数量,进一步促进骨形成。我们的研究表明,干细胞可通过SDF1/CXCR4轴促进其增殖并归巢至股骨,并通过Wnt-1信号进一步帮助骨形成。
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Bone marrow mesenchymal stem cells overexpressing stromal cell- derived factor 1 aid in bone formation in osteoporotic mice.

Background: Osteoporosis is characterized by low systemic bone mineral content and destruction of bone microarchitecture. Promoting bone regeneration and reversing its loss by infusion of exogenous bone marrow mesenchymal stem cells (BMSCs) is a potentially effective treatment for osteoporosis. However, their limited migration to target organs reduces the therapeutic effect of the cells. Stromal cell-derived factor 1 (SDF1) is a chemokine that induces targeted cell migration through the SDF1/CXCR4 (C-X-C chemokine receptor 4) axis and can induce migration of exogenous mesenchymal stem cells to sites of high SDF1 concentration. There are no studies on BMSCs overexpressing SDF1 (SDF1-BMSCs) in osteoporotic mice in vivo. We aimed to investigate if the increased SDF1 concentration facilitated cell migration to the bone.

Methods: We used lentivirus to construct BMSCs overexpressing SDF1 or knocking down CXCR4. We verified the proliferation ability of the cells in vitro using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridinc (BrdU), the migration ability of the cells using Transwell, and the osteogenic and lipogenic ability of the cells using osteogenic and lipogenic induction solutions. In in vivo experiments, we induced osteoporosis in 72 female mice by ovariectomy and injected different groups of cells via the tail vein. Femoral tissue samples were collected for a fixed time, and the osteogenic and homing abilities of the cells were verified by MicroCT and tissue section staining.

Results: We successfully demonstrated that high expression of SDF1 promoted cell proliferation and migration in vitro, without affecting their cell differentiation ability. In an ovariectomized mouse model, SDF1-BMSCs were more likely to be home to the femur than the BMSCs, had a better pro-osteogenic ability, and had higher expression of Wnt-1. Blocking the SDF1/CXCR4 axis reduced the homing of exogenous mesenchymal stem cells (MSCs) to the femur and their osteogenic capacity.

Conclusions: SDF1-BMSCs can further promote bone formation by increasing the number of cells homing to the femur in osteoporotic mice. Our study shows that stem cells can promote their proliferation and home to the femur via the SDF1/CXCR4 axis and further help bone formation via Wnt-1 signaling.

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来源期刊
BMC Musculoskeletal Disorders
BMC Musculoskeletal Disorders 医学-风湿病学
CiteScore
3.80
自引率
8.70%
发文量
1017
审稿时长
3-6 weeks
期刊介绍: BMC Musculoskeletal Disorders is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of musculoskeletal disorders, as well as related molecular genetics, pathophysiology, and epidemiology. The scope of the Journal covers research into rheumatic diseases where the primary focus relates specifically to a component(s) of the musculoskeletal system.
期刊最新文献
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