MATRIX VESICLES AND CALCIFICATION
基质囊泡和钙化
基本信息
- 批准号:6164017
- 负责人:
- 金额:$ 27.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1979
- 资助国家:美国
- 起止时间:1979-01-01 至 2002-02-28
- 项目状态:已结题
- 来源:
- 关键词:annexins bioengineering /biomedical engineering biomaterial development /preparation biomimetics calcification calcium ion chickens chondrocytes computer simulation extracellular matrix proteins laboratory rabbit lipid metabolism liposomes magnesium ion membrane transport proteins molecular cloning molecular dynamics normal ossification nuclear magnetic resonance spectroscopy phospholipase A2 phospholipids phosphorus protein biosynthesis protein reconstitution protein sequence protein structure function sodium ion zinc
项目摘要
The long-range goal of this research is to understand how endochondral
calcification, a process vital for skeletal development and fracture
healing, works. Because isolated matrix vesicles (MV) initiate
calcification by acquiring large amounts of Ca2+ and Pi, they make an
excellent model on which to base the fabrication of clinically useful
biomaterials for stimulating bone healing. Major progress was made
during the past grant period in characterizing the mechanism of MV
mineralization. We have identified and characterized the Ca2+
transporter, made progress in purifying the MV phospholipase A2 and have
laid important groundwork in cloning the Pi transporter. We have
uncovered important information on MV lipid metabolism and in
characterizing the initial mineral phase of MV, and have done
substantial pilot work on reconstitution of the nucleational core and
formation of synthetic MV. Building on these findings, our major goals
for the next grant period are to elucidate how these lipids, proteins
and electrolytes interact to trigger MV formation and mineralization.
Since we have already characterized the Ca2+ porter, lipid, and
electrolyte components of the nucleational complex, we will now
characterize the MV Pi ion porter. Based on the finding of major
changes in lipid composition during MV mineralization, we will now
characterize two enzymes that appear to be responsible for these
changes. During this past grant period we have also acquired a large
body of spectroscopic data on the nature of the nucleational complex.
We will now use this data to guide us in our reconstitution of the
synthetic complex, as well as to deduce its structure using molecular
simulations. Collectively, this body of information will allow us to
precisely construct an implantable biomimetic material for stimulating
bone healing. Our specific aims are: 1) to characterize three new MV
proteins that appear to be critical to MV function, 2) to further
elucidate MV formation, minerals, and metabolism, and 3) to reconstitute
and simulate MV structure and function. Specifically we will
characterize critical interactions that occur between the annexins, PS,
Ca2+ and Pi during MV formation. Also the nature of the first mineral
phase formed by MV and changes in MV lipid composition that accompany
mineralization will be examined. The MV Na+-dependent Pi-transporter,
the phospholipase A2 and the phospholipid base-exchange enzyme will be
identified, cloned and sequenced, and their properties characterized.
The MV nucleational complex will then be synthesized, characterized, and
modeled by computer simulation. Finally, with this information in hand,
functional MV will be reconstituted and tested for bone-healing
properties.
这项研究的长期目标是了解软骨内
项目成果
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ROY E WUTHIER其他文献
ROY E WUTHIER的其他文献
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{{ truncateString('ROY E WUTHIER', 18)}}的其他基金
GORDON RESEARCH CONFERENCE ON CALCIUM PHOSPHATES, 1992
戈登磷酸钙研究会议,1992 年
- 批准号:
2131133 - 财政年份:1992
- 资助金额:
$ 27.29万 - 项目类别:














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