# Aging and dysfunction of progenitor niches: Role of Del-1

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $330,821

## Abstract

Project Summary
The elderly have increased susceptibility to periodontitis, a prevalent inflammatory disease that causes
destruction of the tooth-supporting tissues (periodontium). This increased susceptibility is likely caused by
alterations to the immuno-inflammatory status and/or regenerative potential of the periodontal tissue. Impaired
tissue regeneration may be traced back to age-related alterations in the mesenchymal stem cell (MSC) niche of
the periodontal ligament (PDL), harboring the osteoprogenitors. Del-1 is a homeostatic protein secreted by
distinct tissue resident cells: It regulates the recruitment of neutrophils (endothelial cell-derived Del-1) and the
efferocytosis of apoptotic neutrophils (macrophage-derived Del-1), thus Del-1 controls both the initiation and
resolution of inflammation. Additional research has shown that Del-1 is produced in the PDL and promotes
osteoblastic differentiation as well as induces the formation of new alveolar bone during resolution of
experimental periodontitis. However, Del-1 expression is severely diminished in old age. This project investigates
the overarching hypothesis that the aging-related Del-1 deficiency may contribute to the dysregulation of
osteogenesis, thereby leading to defective periodontal bone regeneration in old age. This proposal comprises
two specific aims and focuses on relevant animal model-based mechanistic and intervention studies, including
mice with lineage-specific deletions or overexpression of Del-1 or its receptor β3 integrin. In Aim 1, it is proposed
that Del-1 promotes osteoblastic differentiation by acting via its RGD motif on β3 integrin in osteolineage
progenitors. Aim 2 involves the elucidation of the mechanisms by which Del-1 regulates osteogenesis in vivo
and, moreover, examines the consequences of aging-related Del-1 deficiency on bone regeneration. It is also
proposed that impaired bone regeneration in old mice can be reversed by local administration of Del-1. On the
basis that the regenerative defect of the aged PDL-MSC niche is reversible and regulated by the extrinsic
microenvironment, the findings of this proposal may potentially pave the way to novel Del-1-based approaches
to rejuvenate niche functionality and thus enhance periodontal bone regeneration in old age.

## Key facts

- **NIH application ID:** 10312010
- **Project number:** 5R01DE028561-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Georgios Hajishengallis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $330,821
- **Award type:** 5
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312010

## Citation

> US National Institutes of Health, RePORTER application 10312010, Aging and dysfunction of progenitor niches: Role of Del-1 (5R01DE028561-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312010. Licensed CC0.

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