MINERALIZATION OF PRIMARY BONE

原始骨或编织骨在几个方面是不同的。在形态学上，原始骨的特征在于其沉积和矿化的速度以及其胶原基质的“解体”。 这种“无组织性”阻碍了详细的结构分析。初级骨暂时取代软的前体组织，是第一个“矿化骨”，占据胚胎的长骨领和颅面骨的部位，愈合骨折，并在适应性骨骼增益响应于增加的生物力学应力。在身体的许多部位，初级骨随后被板层骨取代。 尽管板层骨的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，我们已经发现了一种细胞外生物标志物BAG-75，它专门沉积在注定要成为矿化的原发骨的病灶部位（BMP）。我们的研究结果表明，这发生在体内和体外几个公认的分化成骨细胞培养模型，以及在UMR 106 -01 BSP细胞系。后者的特点是这一过程的速度和形成的大量矿化灶。虽然先前发表的报告可能已将BMP形态学鉴定为晶体影和结节，但缺乏生物标志物减缓了这些部位的表征。我们假设 BMP含有胚胎和愈合骨中矿化过程的初始成核和快速完成所必需的成分。我们的建议将通过审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。将使用啮齿动物骨髓消融模型中产生的原代骨对关键发现进行验证。这项工作的结果应该更好地定义之间的差异，初级和板层骨，以及在诊断和治疗骨质疏松症和动脉粥样硬化的援助。

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.