DETERMINING OSTEOBLAST/BLOOD CELL ADHESION MECHANISMS

造血干细胞分化发生在直接接近 骨髓腔内的成骨细胞。 尽管这一惊人的 联系，令人惊讶的是，很少有人知道精确的细胞和 成骨细胞对骨髓的分子影响 微环境 最近，我们发现人类 成骨细胞I）支持原始人类造血细胞的生长 在长期体外培养中的祖细胞，和ii）人 成骨细胞产生多种细胞因子mRNA。 至今没有 已知的细胞因子单独或组合可以解释所有这些 活动 此外，我们还观察到， 成骨细胞和造血细胞。 为了充分描述 成骨细胞对造血系统的独特贡献 微环境，我们现在提出，以确定哪些细胞粘附 分子被正常的人类造血骨髓利用 祖细胞（CD 34+）在体外与成骨细胞的粘附。 在未来，我们将确定是否炎症介质或 造血细胞的成熟状态改变了它们对 成骨细胞 这些知识，沿着我们的工作， 新的成骨细胞衍生的造血因子，将独特地 为我们进一步研究成骨细胞支持的 造血 这些调查将有助于减少 与骨髓相关的发病率和死亡率 通过增加血液的产生来进行移植手术 细胞，治疗各种骨髓衰竭的首选 包括几种白血病的综合征。 最后是牙槽骨 骨丢失，无论其开始，最终介导的 成骨细胞-破骨细胞相互作用。我们假设 描述了CD 34+细胞粘附于 成骨细胞可能与成骨细胞利用的机制相似 以定位和/或激活骨细胞骨吸收。 因此，在本发明中， 这里确定的机制可能被证明是有用的， 预防口腔组织损失的治疗。

Hematopoietic stem cell differentiation occurs in direct proximity to osteoblasts within the bone marrow cavity. Despite this striking affiliation, surprisingly little is known about the precise cellular and molecular impact of osteoblasts on the bone marrow microenvironment. Recently, we have shown that human osteoblasts I) support the growth of primitive human hematopoietic progenitors in long term in vitro cultures and ii) that human osteoblasts produce a variety of cytokine mRNAs. To date, no known cytokine alone or in combination can account for all of these activities. In addition, we have observed a tight-adhesion between osteoblasts and hematopoietic cells. To fully characterize the unique contributions that osteoblasts make to the hematopoietic microenvironment we now propose to identify which cell adhesion molecules are utilized by normal human hematopoietic bone marrow progenitor cells (CD34+) in their adhesion to osteoblasts in vitro. In the future, we will determine whether inflammatory mediators or the maturational status of hematopoietic cells alters their adhesion to osteoblasts. This knowledge, along with our work in identifying novel osteoblast-derived hematopoietic factors, will uniquely position us for further investigations of osteoblast-supported hematopoiesis. These investigations will be useful in reducing the morbidity and mortality associated with bone marrow transplantation procedures by enhancing the production of blood cells, the treatment of choice for diverse bone marrow failure syndromes including several of the leukemias. Finally alveolar bone loss, regardless of its initiation, is ultimately mediated by osteoblast-osteoclast interactions. We hypothesize that by delineating the mechanisms utilized in by CD34+ cells to adhere to osteoblasts may be similar to the mechanisms utilized by osteoblasts to localize and/or activated osteoclastic bone resorption. As such, the mechanisms identified here may prove useful as potential new therapies for the prevention of oral tissue loss.