# The essential role for mitophagy in osteoblast differentiation

> **NIH NIH P20** · MAINEHEALTH · 2021 · $262,118

## 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 co...

## Key facts

- **NIH application ID:** 10246819
- **Project number:** 5P20GM121301-05
- **Recipient organization:** MAINEHEALTH
- **Principal Investigator:** Anyonya R Guntur
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $262,118
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246819

## Citation

> US National Institutes of Health, RePORTER application 10246819, The essential role for mitophagy in osteoblast differentiation (5P20GM121301-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246819. Licensed CC0.

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