# Muscle regulation of bone function

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $495,503

## Abstract

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.

## Key facts

- **NIH application ID:** 10378491
- **Project number:** 5R01AR073180-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Gerard Karsenty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,503
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378491

## Citation

> US National Institutes of Health, RePORTER application 10378491, Muscle regulation of bone function (5R01AR073180-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378491. Licensed CC0.

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