# Parathyroid hormone (PTH) modulates lipid metabolism in the skeletal niche

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $71,500

## Abstract

PROJECT SUMMARY/ ABSTRACT
The long-term goal of my laboratory is to develop a comprehensive understanding of how intracellular
metabolic pathways impact bone health. Within this scope the current project aims to explore the osteoanabolic
effects of intermittent parathyroid hormone (iPTH} via its modulation of lipid metabolism on cells within
the skeletal niche. Osteoporosis and osteopenia are late-onset diseases affecting a staggering 54 million
people in the U.S. In addition to the financial burden, osteoporosis-related fractures often lead to multiple
comorbidities which significantly reduce longevity. While anabolic agents that increase bone formation such as
PTH or PTH related protein's (PTHrP} have aided in the management of osteoporosis, patients still experience
adverse side-effects. Therefore, continued development of refined therapeutic options is necessary. As such,
this project presents dual, complimentary mechanisms whereby PTH signaling up-regulates lipolysis in bone
marrow adipocytes {BMAdipo}, releasing lipid species into the skeletal niche, while also enhancing fatty acid
oxidation in osteoblasts. Given the intimate proximity of BMAdipo to osteoblasts, it stands to reason that PTH
treatment acts on both BMAdipo to liberate lipid species while also 'priming' the osteoblast to utilize these lipids
as a mechanism capable of supporting the energy demanding process of bone formation. Therefore, our
overarching hypothesis is that PTH's bone anabolic actions involve stimulation of lipolysis in BMAdipo and
enhance fatty acid oxidation in osteoblasts. We will test this hypothesis in two specific aims. The first aim {SA 1}
will determine the ability of PTH-stimulated BMAdipo lipolysis to support PTH-induced bone formation, both in
vivo and in vitro. This will be accomplished using a new mouse model, developed by Co-I, designed to
specifically inhibit lipolysis in BMAdipo. These mice will then be ovariectomized (OVX} or sham-operated on
and be treated with PTH or vehicle control. Skeletal and metabolic parameters will be assessed at the end of
the study. In addition to this experiment, lipid species released from BMAdipo upon PTH treatment will be
characterized using liquid chromatography-mass spectrometry (LC-MS}. The second aim (SA2} will define
PTH's ability to alter osteoblast lipid metabolism via modulation of cellular bioenergetics. Tracing of 13C1a oleic
acid will be performed using LC-MS to determine fatty acid metabolic fate during PTH treatment in osteoblasts.
Additionally, osteoblast mitochondrial oxidative phosphorylation substrate dependency will be measured during
PTH using Seahorse XFe96 technology. Finally, osteoblast bioenergetics will be monitored using reversedphase
high-performance liquid chromatography (RP-HPLC} to determine adenosine monophosphate {AMP},
adenosine diphosphate {ADP}, and ATP flux under control conditions and during PTH stimulation. In summary,
the goal of this project is to enhance our understanding of P...

## Key facts

- **NIH application ID:** 11466947
- **Project number:** 7R01AG069795-06
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Elizabeth Rendina-Ruedy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $71,500
- **Award type:** 7
- **Project period:** 2020-09-30 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11466947

## Citation

> US National Institutes of Health, RePORTER application 11466947, Parathyroid hormone (PTH) modulates lipid metabolism in the skeletal niche (7R01AG069795-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11466947. Licensed CC0.

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