Osteoblast-derived paracrine factors regulate angiogenesis in response to mechanical stimulation.

Osteoblast-derived paracrine factors regulate angiogenesis in response to mechanical stimulation.
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DOI:
10.1039/c6ib00070c
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发表时间:
2016-07-11
期刊:
Integrative biology : quantitative biosciences from nano to macro
影响因子:
--
通讯作者:
Castillo AB
Castillo AB
中科院分区:
其他
文献类型:
--
作者:
Liu C;Cui X;Ackermann TM;Flamini V;Chen W;Castillo AB

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血管生成是指通过内皮细胞的萌发、迁移、增殖和小管形成,从现有的血管中长出新的血管的过程。骨骼生长、动态平衡和修复过程中的血管生成是一个复杂且尚未完全了解的过程。当骨骼适应机械负荷时,我们假设机械刺激在血管生成的背景下调节“骨-血管”串扰。我们发现,与静态培养的成骨细胞条件培养液相比,暴露在流体剪切力下的成骨细胞条件培养液(CM)可促进内皮细胞的增殖和迁移,但不能促进小管的形成。利用模拟血管几何形状的双通道胶原凝胶微流控装置研究内皮细胞的萌发。静态CM可显著增加内皮细胞的萌发频率,而负载CM可显著增加内皮细胞的萌发频率和长度。暴露于相邻通道的流体剪应力下的成骨细胞释放的因子显著增加了发芽频率和发芽长度。成骨细胞释放血管生成因子,其中骨桥蛋白、PDGF-AA、IGBP-2、MCP-1和五角蛋白-3在机械负荷下上调。这些数据表明,在体内,机械力通过调节“骨-血管”串扰来调节骨骼中的血管生成。
Angiogenesis is a process by which new blood vessels emerge from existing vessels through endothelial cell sprouting, migration, proliferation, and tubule formation. Angiogenesis during skeletal growth, homeostasis and repair is a complex and incompletely understood process. As the skeleton adapts to mechanical loading, we hypothesized that mechanical stimulation regulates the “osteo-angio” crosstalk in the context of angiogenesis. We showed that conditioned media (CM) from osteoblasts exposed to fluid shear stress enhanced endothelial cell proliferation and migration, but not tubule formation, relative to CM from static cultures. Endothelial cell sprouting was studied using a dual-channel collagen gel-based microfluidic device that mimics vessel geometry. Static CM enhanced endothelial cell sprouting frequency, whereas loaded CM significantly enhanced both frequency and length. Both sprouting frequency and length were significantly enhanced in response to factors released from osteoblasts exposed to fluid shear stress in an adjacent channel. Osteoblasts released angiogenic factors, of which osteopontin, PDGF-AA, IGBP-2, MCP-1, and Pentraxin-3 were upregulated in response to mechanical loading. These data suggest that in vivo mechanical forces regulate angiogenesis in bone by modulating “osteo-angio” crosstalk.
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