Studies of CD45R/B220+ osteoclast precursor

CD45R/B220破骨细胞前体的研究

• 批准号: 6929113
• 负责人: Joseph A Lorenzo
• 金额: $ 23.78万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929113
• 关键词: B lymphocyte; apoptosis; bone density; bone marrow; cell population study; cell transplantation; cytokine receptors; estrogens; female; hematopoietic stem cells; hormone regulation /control mechanism; interleukin 1; laboratory mouse; osteoclasts; osteoprotegerin; ovariectomy; pathologic bone resorption; stem cells; tissue /cell culture

DESCRIPTION: (provided by applicant) Osteoclasts are unique cells of hematopoietic origin, which possess the capacity to resorb bone. However, the lineages that give rise to osteoclasts are not well described. In preliminary data we found that a highly purified population of murine bone marrow cells expressing the surface marker, CD45R/B220, produced osteoclast-like cells (OCL) after stimulation with M-CSF and RANKL. CD45R1B220 is an antigen that is most often expressed on cells of the B-lymphocyte lineage although it may also be expressed on more immature cells. We have found that ovariectomy increased the number of OCL that formed in cultures of CD45R/B22O+ about bone marrow cells. Examination of RANK expression in bone marrow cells showed that relatively few cells express this protein on their surface. However, treatment with M-CSF in vitro induced expression of RANK mRNA in bone marrow cell cultures. Furthermore, we found that interleukin-l type 1 receptor deficient (IL-1R1-/-) mice, which fail to lose bone mass after ovariectomy, also do not increase the number of OCL that form from CD45R/B220F bone marrow cells after ovariectomy. In addition, in both wild type and IL-1R1-/- mice ovariectomy had no effect on the number of OCL that formed in CD45R1B220- about bone marrow cell cultures. These results imply that estrogen mediates its effects on osteoclast precursor cell number in bone marrow through changes in the CD45R/B220+ osteoclast precursor cell population and that expression of RANK is a critical late event in osteoclastogenesis. The studies of this grant are designed to 1) determine the phenotype of CD45R/B22O+ osteoclast progenitors and their role in ovariectomy induced bone loss and 2) examine the role that RANK expression has in osteoclast formation from CD45R/B220+ about cells.

描述：（由申请人提供）破骨细胞是一种独特的细胞， 造血起源，具有再吸收骨的能力。但 产生破骨细胞的谱系还没有很好的描述。初步 我们发现，高度纯化的小鼠骨髓细胞群 表达表面标志物CD 45 R/B220的细胞产生破骨细胞样细胞（OCL） 用M-CSF和RANKL刺激后。 CD 45 R1 B220是最常表达于肿瘤细胞上的抗原。 B淋巴细胞谱系，尽管它也可以在更不成熟的细胞上表达。 我们发现卵巢切除术增加了OCL形成的数量 CD 45 R/B22 O+骨髓细胞的培养。RANK表达检查 在骨髓细胞中，相对较少的细胞表达这种蛋白质， 他们的表面。然而，在体外用M-CSF处理诱导了 骨髓细胞培养物中的RANK mRNA。 此外，我们发现白细胞介素-1受体1缺陷型（IL-1 R1-/-） 卵巢切除术后没有失去骨量的小鼠， 卵巢切除术后由CD 45 R/B220 F骨髓细胞形成的OCL数量。 此外，在野生型和IL-1 R1-/-小鼠中，卵巢切除术对IL-1 R1的表达没有影响。 在CD 45 R1 B220-约骨髓细胞培养物中形成的OCL的数量。 这些结果表明，雌激素介导其对破骨细胞前体的影响 通过CD 45 R/B220+破骨细胞的变化观察骨髓中的细胞数量 前体细胞群和RANK表达是关键的晚期事件 破骨细胞生成这项研究的目的是1）确定 CD 45 R/B22 O+破骨细胞祖细胞表型及其在 卵巢切除术诱导的骨丢失和2）检查RANK表达的作用， 在破骨细胞形成中，CD 45 R/B220+细胞。