# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · CENTRAL ARKANSAS VETERANS HLTHCARE SYS · 2024 · —

## Abstract

To ensure aging Veterans remain active and mobile with as little musculoskeletal pain as possible, new
approaches to the prevention of osteoporosis and promotion of timely bone regeneration following a fracture are
necessary. This collaborative research study brings together a group of VA investigators with diverse
perspectives, insights, models, and techniques, to synergistically attack a major clinical problem that leads to
high morbidity and mortality among Veterans, a bone fracture. The overall research strategy of each integrated
project is to use pre-clinical models of a disease that either weakens bone or delays bone repair, to investigate
novel ways to enhance the ability of parathyroid hormone (PTH) to promote bone formation, and to assess
disease and treatment effects on bone in a unified, stringent manner. Already under-diagnosed and under-
treated, osteoporosis is likely to increase the number of fragility fractures being treated at VA hospitals without
novel tools for early detection and novel treatment strategies that circumvent the rare but devastating side effects
of current therapies that inhibit bone loss. Addressing this unmet clinical need, the overall aims are to identify
therapeutic strategies to improve bone health among Veterans and to enhance the bone anabolism of PTH
signaling. The collaboration will address this overarching hypothesis: health problems disproportionately
affecting Veterans activate signaling pathways that increase bone resorption, suppress bone formation, or
impede the transition of cartilage to bone in a fracture callus such that improvements in the clinical management
of osteoporosis lie in understanding how these health problems hurt bone health.
This project entitled “PTH receptor Signaling and Diabetes-Induced Bone Disease” will test the hypothesis that
that diabetes (DM) triggers Nox-mediated ROS distress and cholesterol accumulation in bone, which impact
bone formation and material properties; and that these effects are reversed by activation of the PTH Receptor
(PTH1R)/SIK axis in osteocytes. This hypothesis will be tested using a preclinical model of established DM,
bones from diabetic patients, FDA-approved PTH1R ligands PTH and ABL, the orally available SK-124 inhibitor,
and molecular, cellular, and tissue level advanced approaches. Aim 1 will establish the contribution of Nox/ROS
distress and cellular cholesterol accumulation to DM bone disease. We will determine whether DM-induced bone
disease is prevented 1a) by interfering with p22phox-Nox-mediated ROS in mice with loss of function of the
CYBA gene/p22phox protein and/or 1b) by increasing ABCA1-mediated cholesterol efflux pharmacologically with
the liver X receptor (LXR) agonist GW3965. Aim 2 will identify the target cell(s) in bone mediating the crosstalk
between DM and PTH1R/SIK axis. We will establish cell population profiles, gene expression, and
function/pathway enrichment analysis in bone and bone marrow cells, separately, by single ...

## Key facts

- **NIH application ID:** 10925589
- **Project number:** 2IK6BX004596-07
- **Recipient organization:** CENTRAL ARKANSAS VETERANS HLTHCARE SYS
- **Principal Investigator:** Teresita M. Bellido
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2019-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925589

## Citation

> US National Institutes of Health, RePORTER application 10925589, BLRD Research Career Scientist Award Application (2IK6BX004596-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10925589. Licensed CC0.

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