中度机械力刺激通过促进 BMSCs 的定向成骨分化来减轻小鼠的骨丢失。

BACKGROUND: Osteoporosis is a common metabolic bone disease without effective treatment. Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into multiple cell types. Increased adipogenic differentiation or reduced osteogenic differentiation of BMSCs might lead to osteoporosis. Whether static magnetic fields (SMFs) might influence the adipo-osteogenic differentiation balance of BMSCs remains unknown. METHODS: The effects of SMFs on lineage differentiation of BMSCs and development of osteoporosis were determined by various biochemical (RT-PCR and Western blot), morphological (staining and optical microscopy), and micro-CT assays. Bioinformatics analysis was also used to explore the signaling pathways. RESULTS: In this study, we found that SMFs (0.2-0.6 T) inhibited the adipogenic differentiation of BMSCs but promoted their osteoblastic differentiation in an intensity-dependent manner. Whole genomic RNA-seq and bioinformatics analysis revealed that SMF (0.6 T) decreased the PPARγ-mediated gene expression but increased the RUNX2-mediated gene transcription in BMSCs. Moreover, SMFs markedly alleviated bone mass loss induced by either dexamethasone or all-trans retinoic acid in mice. CONCLUSIONS: Taken together, our results suggested that SMF-based magnetotherapy might serve as an adjunctive therapeutic option for patients with osteoporosis.

背景：骨质疏松症是一种常见的代谢性骨病，目前尚无有效治疗方法。骨髓间充质干细胞（BMSCs）具有向多种细胞类型分化的潜能。BMSCs 向脂肪细胞分化增加或向成骨细胞分化减少可能导致骨质疏松症。静磁场（SMFs）是否会影响 BMSCs 的脂肪-成骨分化平衡尚不清楚。

方法：通过各种生化（RT-PCR 和 Western blot）、形态学（染色和光学显微镜）和 micro-CT 检测，确定 SMFs 对 BMSCs 谱系分化和骨质疏松症发展的影响。还进行了生物信息学分析以探索信号通路。

结果：在这项研究中，我们发现 SMFs（0.2-0.6 T）以强度依赖的方式抑制 BMSCs 的脂肪生成分化，但促进其成骨分化。全基因组 RNA-seq 和生物信息学分析表明，SMF（0.6 T）降低了 PPARγ 介导的基因表达，但增加了 BMSCs 中 RUNX2 介导的基因转录。此外，SMFs 显著减轻了地塞米松或全反式维甲酸诱导的小鼠骨量丢失。

结论：综上所述，我们的研究结果表明，基于 SMF 的磁疗可能是骨质疏松症患者的一种辅助治疗选择。