# Assessing the function role of sclerostin in periodontal disease in XLH

> **NIH NIH R03** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $167,527

## Abstract

Project Summary
 X-linked hypophosphatemia (XLH) is the most common form of heritable Rickets, characterized clinically by
impaired skeletal mineralization and low circulating phosphate levels. XLH is caused by a mutation in the
phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX) gene,
which leads to elevated levels of the phosphotropic hormone, fibroblast growth factor 23 (FGF23), and
subsequently renal phosphate wasting. XLH patients also present with a variety of periodontal defects,
including aberrant mineralization of both the alveolar bone and cementum, as well as poor periodontal ligament
attachment. Although novel treatment strategies have been developed that block FGF23 activity and increase
phosphate levels, periodontal disease remains a clinical concern. Our laboratory has recently demonstrated
that sclerostin antibody treatment reduces FGF23 and increases circulating phosphate levels. These systemic
changes were associated with increased bone mass and mineralization levels in the axial skeleton of Hyp
mice. In the current proposal we propose to test the hypothesis that sclerostin is an important mediator of XLH-
related periodontal disease and that suppression of sclerostin activity will improve periodontitis. This
hypothesis is built on published reports describing the importance of sclerostin and Wnt-signaling in the
development of mineralized tissues, including the periodontium. Further, our preliminary data has
demonstrated that sclerostin antibody treatment improves alveolar bone mass and periodontal ligament
attachment in Hyp mice. To test our hypothesis, we will analyze whether suppressing sclerostin activity via
both genetic and pharmaceutical strategies improves the periodontal defects in Hyp mice (Aim 1) and
determine the role of sclerostin in the osteogenic differentiation of dental follicle progenitor cells (DFPCs, Aim
2). If successful, the current proposal will further our understanding of the pathophysiology of periodontitis in
XLH and provide translational data on the use of a sclerostin antibody, a recently FDA-approved
pharmaceutical treatment. Further, the proposal will serve to build the expertise and preliminary data
necessary for Dr. Ross to compete for future R01-level funding in dental and craniofacial research.

## Key facts

- **NIH application ID:** 10303753
- **Project number:** 1R03DE029873-01A1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ryan Dee Ross
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,527
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10303753

## Citation

> US National Institutes of Health, RePORTER application 10303753, Assessing the function role of sclerostin in periodontal disease in XLH (1R03DE029873-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10303753. Licensed CC0.

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