# OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING

> **NIH NIH P01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $89,078

## Abstract

Abstract:
Our society is becoming more and more sedentary, thereby worsening and accelerating the effects of aging. The
central system that is responsible for the beneficial effects of mobility on brain function, cardiac function,
metabolism, and other organs is the musculoskeletal system. Without muscle contraction and bone movement,
there is no exercise and therefore no beneficial effects on the organism. Exercise appears to delay the negative
effects of aging and can ameliorate negative effects of diseases associated with aging. Exercise maintains both
muscle and bone mass and it is most likely the maintenance of the health of the musculoskeletal system that is
responsible for the health of the organism. The hypothesis to be tested includes: Crosstalk occurs between
muscle and bone through systemic factors. The osteocyte is regulated by both mechanical loading and by factors
secreted by contracted muscle. In turn, the osteocyte regulates muscle myogenesis and function. Exercise
targets the osteocyte and muscle by reducing the negative effects of aging. The specific aims of this program
project renewal are 1). Determine how young and old osteocytes regulate myogenesis, muscle mass and
function, 2). Determine how muscle protects and maintains osteoblast/osteocyte viability and function,
3). Examine the role of extracellular vesicles in bone-muscle crosstalk, 4). Determine the role of
estrogen/β-catenin in muscle-bone crosstalk with aging and 5). Determine if exercise can rescue or
reduce the negative effects of aging on bone-muscle crosstalk. These specific aims will be accomplished
through a multidisciplinary approach where bone and muscle biologists interact along with engineers and
biochemists. This program project focuses on bone-muscle crosstalk utilizing muscle and bone transgenic
mouse models, unique bone and muscle cell lines, live cell imaging and intravital imaging capabilities and
integration of metabolomics and lipidomics. The projects and their supporting cores are highly integrative and
will lead to synergistic interactions where the potential for progress and success is greater than the individual
components. Identification of the mechanisms used by muscle and bone to communicate and regulate the
musculoskeletal system as a whole and how these are regulated by exercise should lead to interventions for
musculoskeletal disease, dysfunction, and disorders and prevent the negative effects of immobilization and
aging, not only on the musculoskeletal system, but on the overall health of the individual.

## Key facts

- **NIH application ID:** 11147010
- **Project number:** 3P01AG039355-10S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Lynda F Bonewald
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $89,078
- **Award type:** 3
- **Project period:** 2012-05-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11147010

## Citation

> US National Institutes of Health, RePORTER application 11147010, OSTEOCYTE REGULATION OF BONE/MUSCLE WITH AGING (3P01AG039355-10S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11147010. Licensed CC0.

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