# A new model for spatio-temporal coupling of bone formation and bone resorption governed by osteoclasts

> **NIH NIH R61** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $359,200

## Abstract

ABSTRACT
Osteoporosis is a metabolic bone disorder characterized by progressive decline of bone mass and bone quality,
leading to bone fragility and an increased risk of fracture. Bone mass is tightly controlled by coupling of bone
resorption to bone formation, which is regulated by a cellular communication between bone-destroying cells,
osteoclasts (OCs), and bone-forming cells, osteoblasts (OBs). In this proposed study, we will demonstrate how
OCs regulate OC-to-OB communication by a newly emerged mechanism of cell-cell communication, namely
tunneling nanotube (TNT), and explore the potential preventive therapeutic solutions in skeletal diseases. We
previously reported that disruption of BMP signaling mediated by type 1A receptor (BMPR1A) in OCs
stimulates bone formation by promoting OB differentiation. Together with our preliminary data, we hypothesize
that BMP signaling in OCs regulate TNT formation to locally suppress functions of mature osteoblasts. We will
identify molecules transferred from OCs to OBs via TNT and mechanisms of how OCs recognize mature, but
not immature OBs to communicate. We will also establish a live imaging system in animals to demonstrate
alterations in formation and function of TNTs in conditions mimicking osteoporosis and impacts of drug
treatment such as PTH. Successful completion of the proposed study will pioneer a totally new treatment for
osteoporosis by suppression of TNT formation/function without affecting OC number but to increase bone
formation.

## Key facts

- **NIH application ID:** 10082528
- **Project number:** 1R61AR078073-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yuji MISHINA
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,200
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082528

## Citation

> US National Institutes of Health, RePORTER application 10082528, A new model for spatio-temporal coupling of bone formation and bone resorption governed by osteoclasts (1R61AR078073-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10082528. Licensed CC0.

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