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含硼纳米羟基磷灰石对骨细胞的影响。

The Effect of Boron-Containing Nano-Hydroxyapatite on Bone Cells.

机构信息

Graduate School of Science and Engineering, Department of Bioengineering, Hacettepe University, Ankara, Turkey.

Faculty of Medicine, Department of Medical Biology, Atilim University, Ankara, Turkey.

出版信息

Biol Trace Elem Res. 2020 Feb;193(2):364-376. doi: 10.1007/s12011-019-01710-w. Epub 2019 May 8.

Abstract

Metabolic diseases or injuries damage bone structure and self-renewal capacity. Trace elements and hydroxyapatite crystals are important in the development of biomaterials to support the renewal of bone extracellular matrix. In this study, it was assumed that the boron-loaded nanometer-sized hydroxyapatite composite supports the construction of extracellular matrix by controlled boron release in order to prevent its toxic effect. In this context, boron release from nanometer-sized hydroxyapatite was calculated by ICP-MS as in large proportion within 1 h and continuing release was provided at a constant low dose. The effect of the boron-containing nanometer-sized hydroxyapatite composite on the proliferation of SaOS-2 osteoblasts and human bone marrow-derived mesenchymal stem cells was evaluated by WST-1 and compared with the effects of nano-hydroxyapatite and boric acid. Boron increased proliferation of mesenchymal stem cells at high doses and exhibited different effects on osteoblastic cell proliferation. Boron-containing nano-hydroxyapatite composites increased osteogenic differentiation of mesenchymal stem cells by increasing alkaline phosphatase activity, when compared to nano-hydroxyapatite composite and boric acid. The molecular mechanism of effective dose of boron-containing hydroxyapatite has been assessed by transcriptomic analysis and shown to affect genes involved in Wnt, TGF-β, and response to stress signaling pathways when compared to nano-hydroxyapatite composite and boric acid. Finally, a safe osteoconductive dose range of boron-containing nano-hydroxyapatite composites for local repair of bone injuries and the molecular effect profile in the effective dose should be determined by further studies to validation of the regenerative therapeutic effect window.

摘要

代谢性疾病或损伤会破坏骨结构和自我更新能力。微量元素和羟基磷灰石晶体在支持骨细胞外基质更新的生物材料开发中很重要。在这项研究中,假设负载硼的纳米级羟基磷灰石复合材料通过控制硼的释放来支持细胞外基质的构建,以防止其毒性作用。在这种情况下,通过 ICP-MS 计算了纳米级羟基磷灰石中的硼释放,在 1 小时内大部分硼释放出来,然后以恒定的低剂量持续释放。通过 WST-1 评估了含硼纳米级羟基磷灰石复合材料对 SaOS-2 成骨细胞和人骨髓间充质干细胞增殖的影响,并与纳米羟基磷灰石和硼酸的影响进行了比较。硼在高剂量下增加间充质干细胞的增殖,并对成骨细胞的增殖表现出不同的影响。与纳米羟基磷灰石复合材料和硼酸相比,含硼纳米羟基磷灰石复合材料通过增加碱性磷酸酶活性来增加间充质干细胞的成骨分化。通过转录组分析评估了含硼羟基磷灰石有效剂量的分子机制,并与纳米羟基磷灰石复合材料和硼酸相比,显示其影响与 Wnt、TGF-β 和应激反应信号通路相关的基因。最后,应通过进一步研究确定含硼纳米羟基磷灰石复合材料用于局部修复骨损伤的安全成骨剂量范围和有效剂量的分子作用谱,以验证再生治疗效果窗口。

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