OSTEOCLAST MEDIATED BONE REMODELING

正常的骨重建遵循一个耦合的循环序列，包括 双臂：骨形成和骨形成对吸收的刺激 由于新骨的降解而合成的新骨。相互影响 在局部和全身骨重塑调节通路之间涉及 一个复杂、重叠和多层次的计划，负责平衡 正常的重塑顺序。冗余的监管机制有助于 确保较小的信号偏差不会转化为较大 重塑障碍，如与骨质疏松症和 骨性关节炎。内分泌、自分泌和旁分泌之间的联盟 Signals通过对不断变化的 干细胞和处于不同发育阶段的细胞的种群， 成熟、生理和衰老。许多研究人员正在 探讨成骨细胞和骨髓基质细胞的重要作用 在调节破骨细胞的发育和作用方面。反之， 破骨细胞或相关细胞对体内其他细胞的调节作用 骨的微环境还没有得到太多的关注。这 因此，未被开发的骨生物学领域是 我们计划作为当前的一部分继续进行的研究 求婚。这些研究的主要目标将是测试 破骨细胞可以继续识别和表征的假说 破骨细胞衍生的细胞因子调节成骨细胞的发育和 活性，2)确定其他破骨细胞代谢分泌产物 影响骨形成，3)分析激素、细胞因子和基质- 破骨细胞来源的成骨细胞产生的依赖性调节 调节因子(S)4)研究信号转导机制 参与破骨细胞衍生因子对骨形成的调控； 这里包括的是确定这些因素是否针对亚群 成骨细胞。高纯度禽类破骨细胞，禽类和人类 破骨细胞、鸟类和人类破骨细胞样巨细胞，以及人类 破骨前细胞系FLG 29.1将用于生成 和基质释放产物对人骨髓基质成骨细胞的影响 前体细胞、原代鸡和大鼠成骨细胞以及几种成骨细胞 细胞系。破骨细胞产生的已知细胞因子的调节 看起来影响骨骼信息的信息将被分析和新颖 已确定的因素。新肽因子(S)的cDNA3(S)克隆 从破骨细胞cDNA文库中分离得到。这些研究将改善我们的 了解破骨细胞到成骨细胞的通讯途径，以及 因此，骨的耦合计划的第二个必要的手臂 改建。

Normal bone remodeling follows a coupled cyclical sequence comprised of two arms: the stimulation of resorption in response to bone formation and the synthesis of new bone as a result of its degradation. The interplay between local and systemic bone remodeling regulatory pathways involves a complex, overlapping, and multitiered program responsible for balancing the normal remodeling sequence. Redundant regulatory mechanisms help to ensure that minor signalling aberrations are not translated into major remodeling disorders such as those associated with osteoporosis and osteoarthritis. The alliance between endocrine, autocrine, and paracrine signals orchestrates bone remodeling via effects upon an everchanging population of stem cells and cells in various stages of development, maturation, physiology, and senescence. Many researchers are investigating the important role of osteoblasts and marrow stromal cells in the regulation of osteoclast development and action. Conversely, the modulatory action of osteoclasts or related cells upon other cells within the bone microenvironment has not received much attention. This underexplored area of bone biology is therefore the central theme of the ongoing research that we plan to continue as part of the current proposal. The primary objective of these studies will be to test the hypothesis that osteoclasts can continue to identify and characterize osteoclast-derived cytokines that modulate osteoblast development and activity, 2) identify other osteoclast metabolic secretory products that influence bone formation, 3) analyze the hormonal, cytokine, and matrix- dependent modulation of the production of osteoclast-derived osteoblast regulatory factor(s) 4) examine the signal transduction mechanisms involved in osteoclast-derived factor regulation of bone formation; included here is to determine whether such factors target subpopulations of osteoblasts. Highly purified avian osteoclasts, avian and human osteoclasts, avian and human osteoclast-like giant cells, and the human preosteoclastic cell line FLG 29.1 will be used to generated synthetic and matrix-released products on human marrow stromal osteoblast precursors, primary chick and rat osteoblasts, and several osteoblasts cell lines. The regulation of known cytokines produced by osteoclasts that appear to influence bone information will be analyzed and novel factors identified. cDNA(s) clones for novel peptide factor(s) will be isolated from an osteoclast cDNA library. These studies will improve our understanding of the osteoclast to osteoblast communication pathway, and hence, the second essential arm of the coupling program of bone remodeling.