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MINERALIZATION OF PRIMARY BONE

原生骨的矿化

基本信息

批准号：
7432628
负责人：
JEFFREY Paul GORSKI
金额：
$ 26.07万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-20 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7432628
关键词：
AIDS therapy Ablation Address Adolescent Appearance Appendix Area Atherosclerosis Biochemistry Biological Biological Assay Biological Markers Biomechanics Caliber Calvaria Cell Line Cell model Cells Chronic Disease Clinical Collagen Collagen Fibril Consensus Cultured Cells Data Dental Implants Deposition Development Diagnosis Disease Dissection Electrons Embryo Endopeptidases Environment Erythrocyte Ghost Evaluation Fibroblasts Fibronectin Receptors Fibronectins Figs - dietary Fracture Fracture Healing Freezing Goals Growth Healed Health Human Hydroxyapatites Immature Bone In Vitro Incidence Inorganic Phosphate Transporter Lasers Lead Life Expectancy Location Marrow Mature Bone Mediating Microscopic Microscopy Minerals Modeling Monitor Morphology Nodule Numbers Orthopedics Osteoblasts Osteocalcin Osteogenesis Osteoporosis Pathway interactions Peptide Hydrolases Pharmaceutical Preparations Phase Phosphoproteins Physiologic calcification Prevention Principal Investigator Process Proteins Proteolysis Proteome Proteomics Publications Publishing Rattus Reporting Research Research Personnel Rodent Role Score Seeds Site Skeletal system Specimen Speed Standards of Weights and Measures Stress Structure Testing Time Tissues United States National Institutes of Health Vesicle Work alpha-Fetoproteins base biomineralization bisphosphonate bone bone cell bone healing bone quality bone sialoprotein calcification calcium phosphate clinically significant craniofacial day extracellular fetal healing improved in vivo inhibitor/antagonist insight long bone mineralization novel osteopontin prevent processing speed programs promoter response size tool

项目摘要

Primary or woven bone is distinguished in several respects. Morphologically primary bone is characterized by the speed of its deposition and mineralization, as well as the "disorganization" of its collagenous matrix. This "disorganization" has discouraged detailed structural analyses. Primary bone temporally replaces soft precursor tissue and is the first "mineralized bone" to occupy sites in long bone collars and craniofacial bones of the embryo, in healing fractures, and in adaptive skeletal gain in response to increased biomechanical stress. At many sites in the body, primary bone is subsequently replaced by lamellar bone. Although the mechanism for mineralization of lamellar bone is still controversial, a number of observations strongly suggest that the mechanism regulating primary bone formation and mineralization is distinct. Specifically, we have discovered an extracellular biomarker, BAG-75, that is exclusively deposited at focal sites (BMP) destined to become mineralized primary bone. Our results demonstrate that this occurs both in vivo and in vitro in several well accepted differentiating osteogenic cell culture models, as well as in the UMR106-01 BSP cell line. The latter is distinguished by the speed of this process and the large number of mineralizing foci which form. While prior published reports may have identified BMP morphologically as crystal ghosts and nodules, lack of a biomarker has slowed characterization of these sites. We hypothesize that BMP contain components essential for the initial nucleation and rapid completion of the mineralization process in embryonic and healing bone. Our proposal will test this hypothesis by examining four specific aims. Our experimental strategy will utilize cell culture models to carry out proteomic and functional studies on isolated BMP. Key findings will be validated with primary bone produced in the rodent marrow ablation model. Results of this work should better define the differences between primariy and lamellar bone, as well as aid in the diagnosis and treatment of osteoporosis and atherosclerosis.

原生骨或编织骨在几个方面都有所区别。在形态上，原生骨的特征在于其沉积和矿化的速度，以及其胶原基质的“瓦解”。这种“混乱”阻碍了详细的结构分析。原发骨暂时取代软前体组织，是第一个“矿化骨”，占据胚胎长骨颈和颅面骨中的位置，用于骨折愈合，以及响应增加的生物力学应力的适应性骨骼增益。在身体的许多部位，原生骨随后被板层骨取代。尽管板层骨矿化机制仍存在争议，但大量观察结果强烈表明，调节初级骨形成和矿化的机制是不同的。具体来说，我们发现了一种细胞外生物标志物 BAG-75，它专门沉积在注定会成为矿化初级骨的焦点部位 (BMP)。我们的结果表明，在几种广为接受的分化成骨细胞培养模型以及 UMR106-01 BSP 细胞系中，这种情况在体内和体外均发生。后者的特点是该过程的速度和形成的大量矿化灶。虽然之前发表的报告可能在形态上将 BMP 鉴定为晶影和结节，但缺乏生物标志物减缓了这些位点的表征。我们假设 BMP 含有对于胚胎和愈合骨中初始成核和快速完成矿化过程所必需的成分。我们的提案将通过检查四个具体目标来检验这一假设。我们的实验策略将利用细胞培养模型对分离的 BMP 进行蛋白质组学和功能研究。主要研究结果将通过啮齿动物骨髓消融模型中产生的原代骨进行验证。这项工作的结果应该更好地定义原发骨和板层骨之间的差异，并有助于骨质疏松症和动脉粥样硬化的诊断和治疗。