# Osteoclasts Regulate Osteocyte Viability and Function

> **NIH NIH K01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $103,734

## Abstract

Abstract
Age-related bone loss puts individuals at risk for debilitating fractures that increase the risk for morbidity and
mortality. Osteocytes make up 95% of the skeleton and are increasingly recognized as master regulators of
bone homeostasis. With age there is reduced osteocyte density, and selective deletion of osteocytes results in
osteoporosis. This suggests that maintaining osteocyte viability and function may be an effective strategy to
mitigate age-related bone loss. Osteocytes are well-known to regulate osteoclasts; however, the potential
effects of osteoclasts on osteocytes have not been evaluated. Preliminary data suggest that mice with impaired
osteoclast TGF- signaling exhibit increased osteocyte apoptosis in vivo, and TGF- treated osteoclast
conditioned media protects osteocytes from dexamethasone-induced apoptosis in vitro. A role for osteoclasts
in promoting osteocyte viability and/or function, a relationship supported by my preliminary data, would have
important implications for the majority of osteoporosis therapies that act by reducing osteoclast numbers. The
overall goal of this five year career development application is to test the hypothesis that TGF-β signaling in
osteoclasts induces the production of paracrine factors that promote osteocyte viability necessary to maintain
skeletal homeostasis. Specifically, I will complete the characterization of the osteocyte phenotype in mice with
impaired osteoclast TGF- signaling and evaluate the mechanism by which TGF- signaling in osteoclasts
promotes osteocyte viability in vitro and in vivo. Secondly, I will evaluate the effect of osteoclast
ablation/depletion on osteocytes in mice and humans through genetic (mouse) and pharmacologic (humans)
methods. This proposal offers significant training opportunities in osteocyte phenotyping techniques, including
acid etching/scanning electron microscopy, analysis of the functional response of osteocytes to in vivo axial
loading, as well as direct analysis of osteocyte gene expression without in vitro culture. In addition, studying
the effects of pharmacological depletion of osteoclasts on osteocytes in humans offers valuable experience in
clinical mechanistic research. Correlating the results of animal studies to humans is crucial to advancing basic
findings to the clinic. Therefore, the proposed studies will provide me with training essential to my career
development and lay the ground work for developing an independent R01 application.

## Key facts

- **NIH application ID:** 10017654
- **Project number:** 5K01AR070281-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Megan M. Weivoda
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $103,734
- **Award type:** 5
- **Project period:** 2016-08-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017654

## Citation

> US National Institutes of Health, RePORTER application 10017654, Osteoclasts Regulate Osteocyte Viability and Function (5K01AR070281-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10017654. Licensed CC0.

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