镁离子刺激骨髓基质细胞增强成骨活性，模拟镁合金降解的作用

Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation

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发表状态：

Acta Biomaterialia 10 (2014) 2834–2842

研究团队：

Sayuri Yoshizawa a,b,d, Andrew Brown a,b,c,d, Aaron Barchowsky e, Charles Sfeir a,b,c,d,⇑
a Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA
b The Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA, USA

研究内容：

在本研究中，分析了Mg2+刺激对人骨髓基质细胞(hBMSCs)细胞内信号机制的影响。在含有0.8、5、10、20和100mm MgSO4的培养基中培养hBMSCs。3周后，用茜素红染色分析细胞外基质(ECM)矿化情况，用定量聚合酶链反应阵列分析基因表达情况。接下来，通过分析低氧诱导因子(HIF)-1a和2a (COL10A1的转录因子)、血管内皮生长因子(VEGF) (HIF -2a激活)和过氧化物酶体增殖激活受体共激活因子(PGC)-1a (VEGF的转录共激活因子)的蛋白生成，研究细胞内信号传导的机制。数据表明可能的ECM蛋白和转录因子受Mg2+的影响，负责促进骨再生周围可降解的镁骨科/颅面部设备。

Abstract：

Magnesium alloys are being investigated for load-bearing bone fixation devices due to their initial mechanical strength, modulus similar to native bone, biocompatibility and ability to degrade in vivo.Previous studies have found Mg alloys to support bone regeneration in vivo, but the mechanisms have
not been investigated in detail. In this study, we analyzed the effects of Mg2+ stimulation on intracellular signaling mechanisms of human bone marrow stromal cells (hBMSCs). hBMSCs were cultured in medium containing 0.8, 5, 10, 20 and 100 mM MgSO4, either with or without osteogenic induction factors. After 3 weeks, mineralization of extracellular matrix (ECM) was analyzed by Alizarin red staining, and gene
expression was analyzed by quantitative polymerase chain reaction array. Mineralization of ECM was enhanced at 5 and 10 mM MgSO4, and collagen type X mRNA (COL10A1, an ECM protein deposited during bone healing) expression was increased at 10 mM MgSO4 both with and without osteogenic factors. We also confirmed the increased production of collagen type X protein by Western blotting. Next, we investigated the mechanisms of intracellular signaling by analyzing the protein production of hypoxia-inducible factor (HIF)-1a and 2a (transcription factors of COL10A1), vascular endothelial growth factor (VEGF) (activated by HIF-2a) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1a (transcription coactivator of VEGF). We observed that 10 mM MgSO4 stimulation enhanced COL10A1 and VEGF expression, possibly via HIF-2a in undifferentiated hBMSCs and via PGC-1a in osteogenic cells.These data suggest possible ECM proteins and transcription factors affected by Mg2+ that are responsible for the enhanced bone regeneration observed around degradable Mg orthopedic/craniofacial devices.