MINERALIZATION OF PRIMARY BONE

初级骨或编织骨在几个方面有所区别。在形态上，原生骨的特征是其沉积和矿化的速度，以及其胶原基质的“解体”。 这种“杂乱无章”阻碍了详细的结构分析。初级骨暂时取代了柔软的前体组织，是第一个占据胚胎长骨领骨和颅面骨部位的矿化骨，用于骨折的愈合，以及响应增加的生物力学应力而获得的适应性骨骼。在身体的许多部位，主骨随后被板层骨取代。 尽管板层骨的矿化机制仍然存在争议，但大量的观察结果强烈表明，调控原始骨形成和矿化的机制是明确的。 具体地说，我们发现了一种细胞外生物标记物BAG-75，它专门沉积在注定要成为矿化初级骨的焦点部位(BMP)。我们的结果表明，这在体内和体外都发生在一些公认的分化成骨细胞培养模型中，以及在UMR106-01 BSP细胞系中。后者的区别在于这一过程的速度和形成的大量矿化矿点。虽然先前发表的报告可能从形态上将BMP鉴定为晶体幽灵和结节，但缺乏生物标记物减缓了对这些部位的表征。我们假设 BMP含有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验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。关键的发现将通过在啮齿动物骨髓消融模型中产生的初级骨骼来验证。这项工作的结果应该更好地确定原始骨和板层骨之间的区别，并有助于骨质疏松和动脉粥样硬化的诊断和治疗。

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.