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Cell-Tethered Ligands Modulate Bone Remodeling by Osteoblasts and Osteoclasts

机译:细胞束缚的配体调节成骨细胞和破骨细胞的骨重塑

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摘要

The goals of the present study are to establish an in vitro co-culture model of osteoblast and osteoclast function and to quantify the resulting bone remodeling. The bone is tissue engineered using well-defined silk protein biomaterials in 2D and 3D formats in combination with human cells. Parathyroid hormone (PTH) and glucose-dependent insulinotropic peptide (GIP) are selected because of their roles in bone remodeling for expression in tethered format on human mesenchymal stem cells (hMSCs). The cell-modified biomaterial surfaces are reconstructed from scanning electron microscopy images into 3D models for quantitative measurement of surface characteristics. Increased calcium deposition and surface roughness are found in 3D surface models of silk protein films remodeled by co-cultures containing tethered PTH, and decreased surface roughness is found for the films remodeled by tethered GIP co-cultures. Increased surface roughness is not found in monocultures of hMSCs expressing tethered PTH, suggesting that osteoclast-osteoblast interactions in the presence of PTH signaling are responsible for the increased mineralization. These data point towards the design of in vitro bone models in which osteoblast-osteoclast interactions are mimicked for a better understanding of bone remodeling.
机译:本研究的目的是建立成骨细胞和破骨细胞功能的体外共培养模型,并量化由此产生的骨重塑。使用定义明确的丝蛋白生物材料以2D和3D格式结合人体细胞对组织进行工程改造。选择甲状旁腺激素(PTH)和葡萄糖依赖性促胰岛素肽(GIP)是因为它们在人的间充质干细胞(hMSCs)上以束缚形式表达的骨重构中发挥了作用。从扫描电子显微镜图像将细胞修饰的生物材料表面重建为3D模型,以定量测量表面特征。在通过含有束缚的PTH的共培养物重塑的丝蛋白膜的3D表面模型中,发现钙沉积和表面粗糙度增加,而通过束缚的GIP共培养物的重塑膜的表面粗糙度降低。在表达束缚的PTH的hMSC的单培养中未发现增加的表面粗糙度,这表明在PTH信号存在的情况下破骨细胞-成骨细胞的相互作用是矿化增加的原因。这些数据指向体外骨骼模型的设计,在该模型中模拟了成骨细胞-破骨细胞相互作用,以更好地了解骨骼重塑。

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