骨髓间充质干细胞过表达基质细胞衍生因子 1 有助于骨质疏松症小鼠的骨形成。

Bone marrow mesenchymal stem cells overexpressing stromal cell- derived factor 1 aid in bone formation in osteoporotic mice.

机构信息

Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

First Clinical College, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

出版信息

BMC Musculoskelet Disord. 2024 Nov 4;25(1):878. doi: 10.1186/s12891-024-07957-2.

DOI:10.1186/s12891-024-07957-2

PMID:39497150

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536944/

Abstract

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.

摘要

背景

骨质疏松症的特征是全身骨矿物质含量低和骨微观结构破坏。通过输注外源性骨髓间充质干细胞（BMSCs）促进骨再生和逆转其丢失是治疗骨质疏松症的一种潜在有效方法。然而，它们向靶器官的迁移能力有限，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，通过 SDF1/CXCR4（C-X-C 趋化因子受体 4）轴诱导靶向细胞迁移，并能诱导外源性间充质干细胞向 SDF1 浓度高的部位迁移。目前还没有研究过体内过表达 SDF1 的 BMSCs（SDF1-BMSCs）在骨质疏松症小鼠中的情况。我们旨在研究 SDF1 浓度的增加是否有助于细胞向骨迁移。

方法

我们使用慢病毒构建过表达 SDF1 或敲低 CXCR4 的 BMSCs。我们通过细胞计数试剂盒-8（CCK8）和 5-溴脱氧尿苷（BrdU）检测细胞的体外增殖能力，通过 Transwell 检测细胞的迁移能力，通过成骨和成脂诱导液检测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 只雌性小鼠发生骨质疏松症，并通过尾静脉注射不同的细胞。在固定时间收集股骨组织样本，通过 MicroCT 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 SDF1 的高表达促进了细胞在体外的增殖和迁移，而不影响其细胞分化能力。在去卵巢小鼠模型中，SDF1-BMSCs 比 BMSCs 更有可能归巢到股骨，具有更好的促成骨能力，Wnt-1 的表达更高。阻断 SDF1/CXCR4 轴减少了外源性间充质干细胞（MSCs）归巢到股骨的数量及其成骨能力。