# Role of DMP1 Mediated Paracrine Signaling in Vasculogenesis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $513,225

## Abstract

For dentin repair or regeneration, it is important to have the timely appearance of blood vessels.
Therefore, tissue-engineering strategies to regenerate the dentin-pulp complex require
establishment of vasculature to deliver oxygen, nutrients, hormones, immune cells, minerals
and also help in clearing cellular debris and metabolic waste products during the inflammatory
and regenerative phases of healing. DMP1 (dentin matrix protein1) is a key regulatory protein in
bone and dentin mineralization. We first demonstrated that it has a regulatory role in the
regulation of hydroxyapatite nucleation and growth in the extracellular matrices of bone and
dentin. Subsequently, we demonstrated that DMP1 was localized in the nucleus of
preosteoblasts and preodontoblasts and thus served as a signaling molecule and promoted the
differentiation of these precursor cells. Recently we discovered that DMP1 can stimulate the
release of intracellular calcium in preosteoblasts and preodontoblasts. Depletion of intracellular
calcium from the endoplasmic reticulum leads to ER stress. Cells cope with ER stress by
activating the “Unfolded protein response” (UPR). One of our recent observations is that DMP1
stimulation can promote the secretion of VEGF and other pro-angiogenic factors. Therefore, we
hypothesize that ER stress activated by DMP1 functions to promote the transformation of adult
stem cells such as dental pulp stem cells to endothelial cells and thereby promote
vasculogenesis. In order to determine the mechanism by which DMP1 promotes
vasculogenesis, we will examine the UPR signaling pathway. The UPR is initiated by three ER
transmembrane proteins, of which our preliminary data show that DMP1 stimulation activated
the ATF6 (Activating Transcription Factor 6) arm of the UPR. Accordingly, here we propose to
study the mechanism by which ATF6 mediate transcriptional regulation of VEGF under ER
stress. During dentin repair and regeneration, a major challenge is the maintenance of cell
viability which depends on the availability of a functional vascular system. Accordingly, we will
test the in-vivo vasculogenic competence and therapeutic potential of DMP1 in an in vivo pulp
regeneration model.
Understanding the complex functions of DMP1 could be valuable to develop therapies for
fracture repair in bone or in the tooth to restore lost, damaged or diseased dentin-pulp
complex.

## Key facts

- **NIH application ID:** 10587230
- **Project number:** 1R01DE031737-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Anne George
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $513,225
- **Award type:** 1
- **Project period:** 2022-09-20 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10587230

## Citation

> US National Institutes of Health, RePORTER application 10587230, Role of DMP1 Mediated Paracrine Signaling in Vasculogenesis (1R01DE031737-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10587230. Licensed CC0.

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