# Jawbone is unique: differential responses to growth factor signaling and mechanical loading

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $429,000

## Abstract

ABSTRACT
Craniofacial bone health is important to support eating, speaking, breathing, and expressing emotions, and is
critical to overall health and quality of life. It is known that the jawbone (mandible) is unique because it supports
teeth and shows a higher bone turnover rate than long bones. Our preliminary data described in the next
paragraph further reinforces this notion, especially in response to the loss of BMP signaling and alteration in
the mechano-environment. The FDA has approved recombinant human bone morphogenetic protein-2
(rhBMP-2) for clinical applications in treating skeletal defects and spinal fusions. In dentistry, rhBMP-2 has
been used to augment bone grafts in sinus augmentation and localized alveolar ridge augmentation, which
allows better prosthetic reconstruction. Much of the current knowledge for bone homeostasis is based on
research focused on long bones, including the efficacy of rhBMP-2 treatment. These facts prompted us to
identify unique mechanisms by which osteoblasts of the jaw respond BMP signaling, mechanosensing, and
their crosstalk. Completion of the proposed experiments will provide a unique set of data describing the means
by which osteoblasts in the jawbone may behave differently from those in long bones at a molecular level.
We previously reported that loss of function of Bmpr1a in osteoblasts (cKO), which encodes the type 1A
receptor for BMPs, results in increased trabecular bone mass in long bones, including tibia, spine, and ribs,
due to an imbalance between bone resorption and formation. In the jawbones, however, Bmpr1a cKO leads to
decreased bone mass - an opposite phenotype compared to long bones. The reduction of jawbone mass in the
cKO is rescued by a reduction of masticatory forces, while control mice lose bone mass in this condition.
Therefore, we hypothesize that mechanical loading induced by mastication plays a key role in the differential
response to BMP signaling between jawbones and long bones. We will set up 2 types of unbiased approaches:
1) using single-cell RNA-sequence to compare 2 bones (jaw and tibia) in WT and Bmpr1a cKO with different
mechanoenvironment (soft diet), and 2) using a newly emerged engineered ascorbate peroxidase (APEX2)-
based proximity labeling technology to identify binding proteins to BMPR1A. The advantage of the APEX2
technology is to biotinylate interacting proteins with a 30-second time resolution, therefore, it is ideal for
obtaining alterations of the landscape of interacting proteins following stimulation of growth factors or
mechanical loading, or both. Completing this study will provide novel molecular insight for better physical and
pharmacologic interventions to treat degenerative bone conditions unique to the jawbone such as
osteonecrosis in the jaw and alveolar ridge augmentation by BMPs.

## Key facts

- **NIH application ID:** 10788667
- **Project number:** 1R21DE033500-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yuji MISHINA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10788667

## Citation

> US National Institutes of Health, RePORTER application 10788667, Jawbone is unique: differential responses to growth factor signaling and mechanical loading (1R21DE033500-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10788667. Licensed CC0.

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