Studies of CD45R/B220+ osteoclast precursor

CD45R/B220破骨细胞前体的研究

• 批准号: 6479667
• 负责人: Joseph A Lorenzo
• 金额: $ 27.26万
• 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 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6479667
• 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：(申请人提供)破骨细胞是 造血源，具有吸收骨的能力。然而， 产生破骨细胞的谱系没有得到很好的描述。在预赛中 我们发现一组高度纯化的小鼠骨髓细胞 表达表面标志CD45R/B220可产生破骨细胞样细胞(OCL) 经M-CSF和RANKL刺激后。 CD45R1B220是一种抗原，最常在白血病细胞上表达 B淋巴细胞谱系，尽管它也可能在更不成熟的细胞上表达。 我们发现，卵巢切除增加了OCL形成的数量 CD45R/B22O+对骨髓细胞的培养职级表达的审查 在骨髓细胞中显示，相对较少的细胞在 它们的表面。然而，M-CSF在体外处理后，诱导了 对骨髓细胞培养中的mRNA进行排序。 此外，我们还发现白细胞介素1受体(IL-1R1-/-)缺失。 卵巢切除后未能失去骨量的小鼠也不会增加 卵巢切除后CD45R/B220F骨髓细胞形成的OCL数。 此外，在野生型和IL-1R1-/-小鼠中，卵巢切除对 CD45R1B220中形成的OCL的数量-大约是骨髓细胞培养的数量。 这些结果表明雌激素介导了其对破骨细胞前体的影响。 CD45R/B220+破骨细胞在骨髓中的数量变化 前体细胞群体和等级表达是一个关键的晚期事件 在破骨细胞形成过程中。对这笔赠款的研究旨在1)确定 CD45R/B22O+破骨细胞前体细胞的表型及其在骨髓瘤中的作用 卵巢切除所致的骨丢失和2)检测RANK表达的作用 CD45R/B220+约细胞形成破骨细胞。