# The essential role for mitophagy in osteoblast differentiation

> **NIH NIH P20** · MAINEHEALTH · 2020 · $239,886

## Abstract

Whole body metabolism is regulated by the integration of multiple organ systems, including adipose tissue, the
skeleton, and bone marrow. Imbalance in the regulation of these tissues leads to chronic disorders such as
obesity and osteoporosis. Adipocytes and osteoprogenitor cells share a common mesenchymal precursor, and
link these two highly prevalent diseases. Mesenchymal progenitors are also tightly regulated during aging,
nutritional stress, and rapid temperature shifts. There is growing appreciation that the sympathetic nervous
system plays a unique role in this metabolic regulation, both in health and in disease states. Our overall
program goal is to define specific molecular and signaling pathways that integrate the brain, bone, and adipose
tissue in regulation of metabolic networks. This COBRE program, led by Drs. Lucy Liaw and Clifford Rosen,
brings together four projects that test complementary aspects of adipocyte and skeletal metabolic function, and
their regulation by central nervous system input. Project 1 (A. Brown) will study the role of BMP signaling in
brown adipogenesis and thermogenesis, and will optimize thermogenic capacity in human iPS-derived brown
adipocytes by modifying BMP signaling. This project has high translational significance in relation to obesity
and its related co-morbidities. Project 2 (M. Reagan) addresses the origin and function of bone marrow
adipose tissue, a unique depot that is enhanced in osteoporosis and obesity, and may contribute to skeletal
fragility. This project will test the novel hypothesis that osteocyte-derived sclerostin promotes marrow
adipogenesis via inhibition of Wnt signaling, and will utilize bioengineering approaches and mouse models of
altered bone physiology. Project 3 (C. Duarte) is a translational project addressing the consequences of
atypical antipsychotics on bone fracture risk. Atypical antipsychotics such as risperidone (RIS) are highly
prescribed for psychiatric and behavioral symptoms, and have side effects that include bone loss, increased
fracture risk, and weight gain. This project will study nursing home residents, including prevalent users of RIS
and β-blockers, which alone show a protective effect on bone loss in animal studies. This project will determine
if the combination of RIS and β-blockers reduce the risk of fracture compared to RIS alone. Project 4 (K.
Motyl) is complementary to Project 3, and uses mouse models to test the novel hypothesis that RIS acts on
the central nervous system to target bone loss directly or via activation of brown adipose tissue. This project
proposes novel analyses of RIS in brain regions that innervate bone, and also tests the hypothesis that RISinduced
activation of brown adipose tissue can, in turn, mediate bone loss. These projects will be supported by
an Administrative and Professional Development Core that emphasizes scientific collaboration and continued
professional development, and three scientific cores: (i) Proteomics and Lip...

## Key facts

- **NIH application ID:** 10084622
- **Project number:** 5P20GM121301-04
- **Recipient organization:** MAINEHEALTH
- **Principal Investigator:** Anyonya R Guntur
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $239,886
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084622

## Citation

> US National Institutes of Health, RePORTER application 10084622, The essential role for mitophagy in osteoblast differentiation (5P20GM121301-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10084622. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*