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Muscle regulation of bone function

肌肉对骨功能的调节

基本信息

批准号：
10378491
负责人：
Gerard Karsenty
金额：
$ 49.55万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10378491
关键词：
Acute Address Affect Age B Cell Proliferation Binding Biological Biology Blood Circulation Bone Matrix Bone Resorption Bone remodeling Cell Culture Techniques Cell model Cells Cellular biology Chronic Drops Endocrine Endocrine Glands Environment Exclusion Exercise Feedback Foundations Future GPRC6A gene Goals Homeostasis Hormonal Hormones Human Injections Insulin Interleukin 6 Receptor Interleukin-6 Laboratories Life Metabolic Metabolic Diseases Molecular Mus Muscle Muscle Fibers Muscle function Muscular Atrophy Mutant Strains Mice Myoblasts Organ Osteoblasts Osteocalcin Osteoclasts Osteocytes Pancreas Pathway interactions Peritoneal Physiological Processes Pituitary Gland Play Production Recombinants Regulation Research Rest Role Running Signal Transduction Skeletal Muscle Skeleton Source Structure of beta Cell of islet Suggestion Testing Time Wild Type Mouse Work base blood glucose regulation bone bone cell bone loss bone mass cell type efficacy testing exercise capacity experimental study improved in vivo insulin secretion insulin sensitivity mouse model novel peptide hormone receptor response translational study treadmill

项目摘要

Project Summary The influence of muscle derived molecules on bone remodeling has been for a long time a topic of intense research in bone biology. Recently we have provided suggestive evidence that interleukin-6 (IL-6) synthesized in, and secreted in the general circulation by myoblasts, is a powerful and positive regulator of the release of the bone-derived hormone osteocalcin. Moreover, classical studies of bone cell biology had proposed twenty five years ago that IL-6 may regulate osteoclast differentiation and some aspects of bone remodeling. In view of both of these classical and more recent observations, the question arises as to know whether muscle-derived IL-6 is a biologically important regulator of bone remodeling at rest or during exercise, in young and/or older mice. A second question is to know whether muscle-derived IL-6 is a significant regulator in vivo of the release of osteocalcin and therefore of the biological activity of this osteoblast-specific secreted molecule. We intend to address these two related questions of bone biology in vivo and through the use of several mouse models of cell-specific deletion for either IL-6 in myoblasts or its receptor in osteoblasts, osteocytes and osteoclasts. To achieve these goals, the Specific Aims of this application are: - Determine the role of muscle-derived IL-6 in regulating exercise response and bone mass in vivo. - Delineate the relative influence of IL-6 signaling in cells of the osteoblast or the osteoclast lineage on exercise capacity and bone mass in vivo. - Determine whether acute or chronic delivery of recombinant osteocalcin is sufficient to increase exercise capacity in wild-type mice as they age.

项目总结