Centre for the Cellular Microenvironment, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK.
SUPA Department of Biomedical Engineering, University of Strathclyde, Glasgow, G1 1QE, UK.
Sci Rep. 2021 Nov 23;11(1):22741. doi: 10.1038/s41598-021-02139-9.
Models of bone remodelling could be useful in drug discovery, particularly if the model is one that replicates bone regeneration with reduction in osteoclast activity. Here we use nanovibrational stimulation to achieve this in a 3D co-culture of primary human osteoprogenitor and osteoclast progenitor cells. We show that 1000 Hz frequency, 40 nm amplitude vibration reduces osteoclast formation and activity in human mononuclear CD14 blood cells. Additionally, this nanoscale vibration both enhances osteogenesis and reduces osteoclastogenesis in a co-culture of primary human bone marrow stromal cells and bone marrow hematopoietic cells. Further, we use metabolomics to identify Akt (protein kinase C) as a potential mediator. Akt is known to be involved in bone differentiation via transforming growth factor beta 1 (TGFβ1) and bone morphogenetic protein 2 (BMP2) and it has been implicated in reduced osteoclast activity via Guanine nucleotide-binding protein subunit α13 (Gα13). With further validation, our nanovibrational bioreactor could be used to help provide humanised 3D models for drug screening.
骨重建模型在药物发现中可能很有用，特别是如果该模型可以复制具有降低破骨细胞活性的骨再生。在这里，我们使用纳米振动刺激在原代人成骨祖细胞和破骨细胞祖细胞的 3D 共培养物中实现这一目标。我们表明，1000Hz 频率、40nm 振幅的振动可减少单核人 CD14 血液细胞中的破骨细胞形成和活性。此外，这种纳米级振动既能增强原代人骨髓基质细胞和骨髓造血细胞共培养物中的成骨作用，又能减少破骨细胞的形成。此外，我们使用代谢组学来鉴定 Akt（蛋白激酶 C）作为潜在的介质。Akt 已知通过转化生长因子β 1（TGFβ1）和骨形态发生蛋白 2（BMP2）参与骨分化，并且通过鸟嘌呤核苷酸结合蛋白亚基α13（Gα13）参与降低破骨细胞活性。经过进一步验证，我们的纳米振动生物反应器可用于帮助提供用于药物筛选的人源化 3D 模型。
