MOLECULAR AND CELLULAR MECHANISMS OF OSTEOPOROSIS

骨质疏松症的分子和细胞机制

• 批准号: 2862165
• 负责人: STAVROS C. MANOLAGAS
• 金额: $ 5.11万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-27 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2862165
• 关键词: aging; bone density; bone development; osteoblasts; osteopenia; physiologic bone resorption

The central hypothesis of the Program is that the balance between bone resorption and bone formation depends more on the number of bone cells carrying out these processes than on the individual capacities involved. The goal is to further the understanding of osteoporosis by elucidating the molecular, cellular, and genetic mechanisms of bone loss following loss of gonadal function and during aging. In accordance with the central hypothesis, it is proposed that the former is due mainly to excessive osteoclastogenesis and the latter mainly to inadequate osteoblastogenesis. To achieve this goal, three projects, supported by three cores, have been planned. A Project will test the hypothesis that IL/6, and other members of the same cytokine subfamily that share the gp130 signal transducer, are under the inhibitory control of sex steroids, and stimulate osteoblast as well as osteoclast development; a novel mechanism of coupling based on a parallel rather than a serial signal pathway. Another Project will attempt to establish a causal relationship between osteoblastogenesis, bone formation, and bone mass, comparing the SAM P6 and SAM R1 mouse, and determine the relative importance of decreased osteoblast progenitor formation in the bone marrow, and premature osteoblast apoptosis. Another Project will determine the heritability of bone density (measured by DEXA) in the SAM P6 and R1 mouse strains by cross-breeding and comparing the F1 and F2 progeny. Microsatellite repeat markers that distinguish between the P6 and R1 genomes will be used to map and eventually isolate genes associated with osteopenia. One Core will provide scientific, biostatistical, and administrative support to the entire program. One Core will maintain a supply of well-defined animal strains for each investigator. Another Core will provide bone densitometry and bone histomorphometry, both traditional and molecular.

该程序的中心假设是骨头之间的平衡 吸收和骨形成更多地取决于骨细胞的数量 进行这些过程比所涉及的个人能力。 目的是通过阐明，进一步了解骨质疏松症 骨质流失的分子，细胞和遗传机制 性腺功能和衰老期间的丧失。 按照中央 假设，建议前者主要是由于过度造成的 破骨细胞生成和后者主要是不充分的成骨细胞生成。 为了实现这一目标，三个核心支持的三个项目已经 计划。 一个项目将检验IL/6和其他成员的假设 共享GP130信号传感器的同一细胞因子亚家族中 在性类固醇的抑制性控制下，并刺激成骨细胞 以及破骨细胞的发展；基于A的新型耦合机制 平行而不是串行信号途径。 另一个项目将 试图在成骨细胞生成之间建立因果关系， 比较SAM P6和SAM R1小鼠的骨形成和骨骼质量，以及 确定成骨细胞祖细胞减少的相对重要性 骨髓形成和成骨细胞凋亡。 其他 项目将确定骨密度的遗传力（由DEXA测量） 在SAM P6和R1小鼠菌株中，通过交叉繁殖和比较F1 和F2后代。 微卫星重复标记 P6和R1基因组将用于绘制并最终分离基因 与骨质减少症相关。 一个核心将提供科学， 生物统计学和对整个计划的行政支持。 一 核心将为每种供应供应明确的动物菌株 研究者。 另一个核心将提供骨密度测定法和骨骼 传统和分子的组织形态测定法。