Studies of CD45R/B220+ osteoclast precursor

CD45R/B220破骨细胞前体的研究

• 批准号: 6789954
• 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/6789954
• 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）破骨细胞是独特的单元 造血起源，具有吸收骨骼的能力。但是， 产生破骨细胞的谱系未充分描述。在初步 数据我们发现高度纯化的鼠骨髓细胞群 表达表面标记CD45R/B220产生了破骨细胞样细胞（OCL） 用M-CSF和RANKL刺激后。 CD45R1B220是一种抗原，最常在细胞上表达 B淋巴细胞谱系也可以在更未成熟的细胞上表达。 我们发现卵巢切除术增加了在 关于骨髓细胞的CD45R/B22O+的培养物。 rank 在骨髓细胞中，相对较少的细胞在 他们的表面。但是，用M-CSF在体外诱导的表达 骨髓细胞培养物中的mRNA。 此外，我们发现白介素L型1受体缺陷（IL-1R1 - / - ） 卵巢切除术后未能失去骨骼的小鼠也不会增加 卵巢切除术后CD45R/B220F骨髓细胞的OCL数量。 此外，在野生型和IL-1R1 - / - 小鼠卵巢切除术中均未影响 在CD45R1B220中形成的OCL数量 - 关于骨髓细胞培养物。 这些结果表明，雌激素介导了其对破骨细胞前体的影响 通过CD45R/B220+破骨细胞的变化，骨髓中的细胞数 前体细胞种群和等级的表达是关键的晚期事件 在破骨细胞生成中。该赠款的研究设计为1）确定 CD45R/B22O+破骨细胞祖细胞的表型及其在 卵巢切除术诱导的骨质流失，2）检查等级表达的作用 在CD45R/B220+细胞的破骨细胞形成中。