# ROLE OF OSTEOCLAST PRECURSORS IN PERIODONTAL BONE LOSS

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $352,688

## Abstract

Project Summary
Excessive activity of osteoclasts (OC), the body's sole bone resorbing cells, is a major characteristic of
pathogenic bone loss in periodontitis. Although a great deal is known about the process of OC differentiation,
the identity of OC precursors (OCP) in vivo, and their role in periodontitis remain scarce, especially in aging
where the extent of bone loss is increased. Recent studies have identified a cell cycle-arrested quiescent OCP
present in very low numbers. These cells are receptor activator of NF-κB (RANK)-positive and express colony-
stimulating factor-1 receptor (c-fms) at various levels, but scarcely express monocyte/macrophage/ granulocyte
markers. Using in vivo mouse models, we have shown that infection with the periodontal-associated pathogen
Porphyromonas gingivalis (Pg) induces the expansion of an earlier stage c-fms+RANK- OCP (eOCP) and the
more advanced stage RANK+ OCP (rOCP) in bone marrow and spleen. In addition, eOCP and rOCP potently
suppress CD4+ T cell proliferation in vitro, highlighting an important role of OCP in immune regulation.
Moreover, compared to young mice, old mice show increased periodontal bone loss, as well as increased OCP
frequency and osteoclastogenic potential, suggesting that increased OCP pool underlies host susceptibility to
periodontal bone loss in aging. Based on our preliminary studies and published work, we hypothesize that Pg
infection results in the expansion of OCP that can be shunted toward OC formation and bone loss at the
infection/inflammation sites, while at the same time dampen host immune responses, which is beneficial for the
persistence of infection and maintenance of chronic inflammation. We will test our hypothesis by pursuing two
specific aims: 1) Delineate the regulation of OCP following Pg infection; 2) Determine the effect of OCP on host
immune responses and bone loss in vivo to Pg infection. Our proposed studies will provide novel and
significant insight into the pathogenesis of Pg infection and periodontitis leading to the potential development of
targeted therapeutics for inflammatory bone loss diseases.

## Key facts

- **NIH application ID:** 10201568
- **Project number:** 5R01DE026465-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Ping Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,688
- **Award type:** 5
- **Project period:** 2017-07-17 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201568

## Citation

> US National Institutes of Health, RePORTER application 10201568, ROLE OF OSTEOCLAST PRECURSORS IN PERIODONTAL BONE LOSS (5R01DE026465-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201568. Licensed CC0.

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