Role of erythropoietin in skeletal muscle and bone maintenance and repair

促红细胞生成素在骨骼肌和骨骼维护和修复中的作用

• 批准号: 9148746
• 负责人: Constance Noguchi
• 金额: $ 49.45万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9148746
• 关键词: Adipocytes; Affect; Bone Density; Bone Development; Bone Marrow; Bone Resorption; Bone remodeling; Cell Survival; Chronic; Data; Erythrocytes; Erythroid Progenitor Cells; Erythropoietin; Erythropoietin Receptor; Exhibits; Femur; Hematocrit procedure; Hematopoietic; Maintenance; Marrow; Mus; Muscle; Muscle Fibers; Myoblasts; Osteoblasts; Osteoclasts; Production; Reporting; Role; Signal Transduction; Site; Skeletal Muscle; Skeletal bone; Staining method; Stains; Tissues; Transgenic Organisms; bone; bone healing; improved; macrophage; mouse model; osteoclastogenesis; precursor cell; progenitor; repaired; response; substantia spongiosa

Expression of erythropoietin receptor in select non-hematopoietic tissue provides for erythropoietin response beyond erythroid progenitor cell survival, proliferation and differentiation. Bone marrow is the primary site of erythropoietin activity and erythropoietin effects on bone remodeling have been reported to be associated with both improved bone healing as well as with bone resorption. We observed that in addition to the increase in hematocrit, erythropoietin treatment in mice decreased trabecular bone mineral density and trabecular number, and increased trabecular spacing. Mice with chronic elevated erythropoietin also exhibited decreased trabecular bone and cortical bone. Increased TRAP stained osteoclasts were observed in femur sections from these mice and enhanced osteoclastogenesis in corresponding whole bone marrow cultures. These data provide evidence that in the bone marrow, increased erythropoietin stimulated hematopoietic activity is accompanied by erythropoietin stimulated bone remodeling with decreased trabecular bone mineral density. The marrow space expands as a consequence of the increased bone resorption.

红细胞生成组织中红细胞生成素受体的表达可为红细胞祖细胞存活，增殖和分化以外的红细胞生成素反应。据报道，骨髓是促红细胞生成素活性的主要部位，促红细胞生成素对骨重塑的作用与改善的骨骼愈合以及骨吸收有关。我们观察到，除血细胞比容的增加外，小鼠中红细胞生成素治疗降低了小梁骨矿物质的密度和小梁数量，并增加了小梁间距。慢性红细胞生成素的小鼠也表现出降低的小梁骨和皮质骨。在这些小鼠的股骨切片中观察到陷阱染色增加的破骨细胞，并在相应的整个骨髓培养物中增强了破骨细胞生成。这些数据提供了证据表明，在骨髓中，促红细胞生成素刺激的造血活性伴随着促红细胞生成素刺激的骨重塑，而小梁骨矿物质密度降低。骨髓空间由于骨吸收增加而扩大。

项目成果

Erythropoietin contributes to slow oxidative muscle fiber specification via PGC-1α and AMPK activation.

• DOI: 10.1016/j.biocel.2013.03.007
• 发表时间: 2013-07
• 期刊: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
• 影响因子: 4
• 作者: Wang, Li;Jia, Yi;Rogers, Heather;Suzuki, Norio;Gassmann, Max;Wang, Qian;McPherron, Alexandra C.;Kopp, Jeffery B.;Yamamoto, Masayuki;Noguchi, Constance Tom
• 通讯作者: Noguchi, Constance Tom