# Role of Glutamine Metabolism during Osteoblast Differentiation and Bone Formation

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $178,998

## Abstract

Project Summary:
Glutamine is a conditionally essential amino acid that has myriad uses in the cell. Aside from direct
incorporation into protein, glutamine can be metabolized to generate nucleotides, other amino acids, ATP after
anaplerosis into the TCA cycle, and glutathione to protect against oxidative stress. It is unknown how
osteoblasts utilize glutamine and when it is required during differentiation. We recently identified glutaminase
(GLS) as a critical regulator of Wnt dependent pathological bone formation. GLS deaminates glutamine to
form glutamate, the first step in glutamine metabolism. Using a pharmacological approach, we demonstrated
GLS activity was required for bone formation in the LRP5 human high bone mass disease mouse model.
Importantly, GLS inhibition did not affect bone mass in otherwise wild type mice indicating GLS and glutamine
metabolism may not be required for physiological bone formation in mice. In this proposal, we will 1) establish
the necessity and sufficiency of glutaminase (GLS) to regulate osteoblast differentiation and bone formation, 2)
determine if the molecular regulation of GLS activity by WNT, and 3) understand how glutamine is metabolized
in mesenchymal stem cells. Our findings will have broad implications in bone development, maintenance of
bone mass, skeletal repair and regeneration, as well as identify if stimulating glutamine metabolism is a viable
osteoanabolic target to stimulate bone formation.

## Key facts

- **NIH application ID:** 9897618
- **Project number:** 5R01AR071967-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Courtney Michael Karner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,998
- **Award type:** 5
- **Project period:** 2018-04-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897618

## Citation

> US National Institutes of Health, RePORTER application 9897618, Role of Glutamine Metabolism during Osteoblast Differentiation and Bone Formation (5R01AR071967-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897618. Licensed CC0.

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