DETERMINING OSTEOBLAST/BLOOD CELL ADHESION MECHANISMS

造血干细胞分化发生在直接靠近 骨髓腔内的成骨细胞。尽管这令人震惊 从属关系，令人惊讶的是，人们对确切的细胞和 成骨细胞对骨髓的分子影响 微环境。最近，我们已经证明了人类 成骨细胞支持原始人类造血细胞的生长 长期体外培养的祖细胞和II)人类 成骨细胞产生多种细胞因子mRNAs。到目前为止，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，我们还观察到了一种紧密的粘连 成骨细胞和造血细胞。要全面描述 成骨细胞对造血的独特贡献 微环境我们现在建议识别哪种细胞黏附 分子被正常的人造血骨髓利用 祖细胞(CD34+)在体外与成骨细胞的黏附。 在未来，我们将确定炎症介质或 造血细胞的成熟状态改变了它们与 成骨细胞。这一知识，以及我们在识别 新型成骨细胞来源的造血因子，将独一无二 为成骨细胞支持的进一步研究做好准备 造血术。这些调查将有助于减少 与骨髓相关的发病率和死亡率 通过增加血液产量来进行移植手术 细胞，治疗各种骨髓衰竭的选择 症状包括几种白血病。最后牙槽骨 骨丢失，无论它是如何开始的，最终都是由 成骨细胞-破骨细胞的相互作用。我们假设，通过 CD34+细胞黏附机制的研究 成骨细胞可能与成骨细胞利用的机制相似 定位和/或激活破骨细胞性骨吸收。因此， 这里确定的机制可能被证明是有用的潜在的新的 预防口腔组织丢失的治疗方法。

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.