Fluid shear stress and endothelial cells synergistically promote osteogenesis of mesenchymal stem cells via integrin β1-FAK-ERK1/2 pathway.

Turkish journal of biology = Turk biyoloji dergisi Pub Date : 2021-12-14 eCollection Date: 2021-01-01 DOI:10.3906/biy-2104-20
Mingli Jiang, Qihua Shen, Yi Zhou, Wenxia Ren, Miaomiao Chai, Yan Zhou, Wen-Song Tan
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引用次数: 6

Abstract

Prevascularization and mechanical stimulation have been reported as effective methods for the construction of functional bone tissue. However, their combined effects on osteogenic differentiation and its mechanism remain to be explored. Here, the effects of fluid shear stress (FSS) on osteogenic differentiation of rat bone-marrow-derived mesenchymal stem cells (BMSCs) when cocultured with human umbilical vein endothelial cells (HUVECs) were investigated, and underlying signaling mechanisms were further explored. FSS stimulation for 1-4 h/day increased alkaline phosphatase (ALP) activity and calcium deposition in coculture systems and promoted the proliferation of cocultured cells. FSS stimulation for 2 h/day was selected as the optimized protocol according to osteogenesis in the coculture. In this situation, the mRNA levels of ALP, runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), and protein levels of OCN and osteopontin (OPN) in BMSCs were upregulated. Furthermore, FSS and coculture with HUVECs synergistically increased integrin β1 expression in BMSCs and further activated focal adhesion kinases (FAKs) and downstream extracellular signal-related kinase (ERK), leading to the enhancement of Runx2 expression. Blocking the phosphorylation of FAK abrogated FSS-induced ERK phosphorylation and inhibited osteogenesis of cocultured BMSCs. These results revealed that FSS and coculture with HUVECs synergistically promotes the osteogenesis of BMSCs, which was mediated by the integrin β1-FAK-ERK signaling pathway.

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流体剪切应力与内皮细胞通过整合素β1-FAK-ERK1/2通路协同促进间充质干细胞成骨。
预血管化和机械刺激已被报道为构建功能性骨组织的有效方法。然而,它们对成骨分化的共同作用及其机制仍有待探讨。本文研究了流体剪切应力(FSS)对大鼠骨髓间充质干细胞(BMSCs)与人脐静脉内皮细胞(HUVECs)共培养成骨分化的影响,并进一步探讨了潜在的信号机制。FSS刺激1 ~ 4 h/d可提高共培养系统中碱性磷酸酶(ALP)活性和钙沉积,促进共培养细胞的增殖。根据共培养成骨情况,选择FSS刺激2 h/d作为最佳方案。在这种情况下,骨髓间充质干细胞中ALP、Runx2、骨钙素(OCN) mRNA水平以及OCN、骨桥蛋白(OPN)蛋白水平上调。此外,FSS与HUVECs共培养可协同提高BMSCs中整合素β1的表达,并进一步激活局灶黏附激酶(FAKs)和下游细胞外信号相关激酶(ERK),导致Runx2表达增强。阻断FAK磷酸化可消除fss诱导的ERK磷酸化,抑制共培养BMSCs的成骨。这些结果表明,FSS与HUVECs共培养可协同促进BMSCs的成骨,这是由整合素β1-FAK-ERK信号通路介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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