权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanical response of osteoblasts in 3D matrix

3D 矩阵中成骨细胞的机械响应

基本信息

批准号：
7215630
负责人：
Hiroki Yokota
金额：
$ 19.48万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-12 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7215630
关键词：
Address Adherens Junction Affect Biological Assay Calcium Canis familiaris Cell Communication Cell Density Cell Proliferation Cells Cellular Morphology Collagen Collagen Type I Communication Connective Tissue Culture Media Cultured Cells Deposition Devices Disruption Dominant-Negative Mutation Endopeptidases Environment Exhibits Extracellular Matrix Family Frequencies Gap Junctions Genes In Situ In Vitro Intercellular Junctions Knowledge Liquid substance Matrix Metalloproteinases Measures Mechanics Messenger RNA Microfilaments Microscope Microscopy Monitor Nutrient Osteoblasts Peptide Hydrolases Polymerase Chain Reaction Proliferating Property Proteins Pump Reverse Transcriptase Polymerase Chain Reaction Role Slide Speed Stimulus Stress Surface System Testing Time Tissue Engineering Tubular formation Walking Western Blotting base bone cDNA Arrays fluid flow inhibitor/antagonist insight intercellular communication mRNA Expression mineralization novel osteopontin response size surface coating

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of the proposed project is to elucidate the role of mechanotransduction in bone adaptation. Depending on their substrate geometries, osteoblasts grow and develop differently in the in vitro culturing system. Compared to the cells cultured on 2D surface, osteoblasts grown in a 3D matrix exhibit slower cellular proliferation and enhanced calcium deposition. The observed difference raises a question on the role of substrate geometries in the osteoblastic responses to mechanical stimuli. Our current in vitro knowledge on mechanotransduction is mostly based on the osteoblasts grown on a flat substrate. We recently developed a novel mechanical loader with a piezoelectric actuator suitable for applying strain and fluid flow to osteoblasts grown in the 3D porous collagen matrix. The mechanical loader is capable of generating strain in any waveform and strain-induced fluid flow in tubular collagen pores in the matrix. Using this mechanical loader, the proposed project aims to investigate the responses of osteoblasts in the 3D collagen matrix, and the role of intercellular contacts in mechanotransduction, especially the role of gap junctions and actin filaments. Three specific aims of the proposed project are to (i) identify the specific waveforms most effective in inducing mechanotransduction (ii) compare the responses to strain, strain-induced fluid flow, and global chemotransport of osteoblasts grown in the 2D and 3D culturing systems, and (iii) examine the role of gap junctions and actin filaments in mechanotransduction in the 3D matrix. In assaying the responses to mechanical stimuli, mRNA levels, protein levels, and proteolytic activities of the genes sensitive to strain/ stress will be determined using the strain waveform measured in dogs during walking. The mRNA level will be determined by cDNA array as well as RT-PCR, and the protein level will be determined by Western analysis. Activity of matrix metalloproteinases, a family of proteolytic enzymes responsive to mechanical stimuli, will be assayed using fluorescent fibril degradation and zymography. Pharmacological inhibitors and dominant negative mutants will be used to disrupt intercellular communications. Completion of these studies should provide significant insight into the mechanical responses of osteoblasts in a 3D environment, and contribute to developing. q load-induced in vitro connective tissue engineering.

描述（由申请人提供）：

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Artificial ants deposit pheromone to search for regulatory DNA elements.

DOI：
10.1186/1471-2164-7-221
发表时间：
2006-08-30
期刊：
BMC GENOMICS
影响因子：
4.4
作者：
Liu, Yunlong;Yokota, Hiroki
通讯作者：
Yokota, Hiroki

Model-based comparative prediction of transcription-factor binding motifs in anabolic responses in bone.

DOI：
10.1016/s1672-0229(08)60003-0
发表时间：
2007-12
期刊：
GENOMICS PROTEOMICS & BIOINFORMATICS
影响因子：
9.5
作者：
Chen, Andy B.;Hamamura, Kazunori;Wang, Guohua;Xing, Weirong;Mohan, Subburaman;Yokota, Hiroki;Liu, Yunlong
通讯作者：
Liu, Yunlong

A brief review of bone adaptation to unloading.