# Adenosine A2B Receptor in Bone Health and Osteoporosis

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $473,823

## Abstract

ABSTRACT
Bone is a highly dynamic organ that undergoes continuous remodeling and maintains a balance between bone
formation and resorption. Bone cells, osteoblasts, which contribute to new bone formation, and osteoclasts,
which resorb bone tissue, act in concert to maintain bone homeostasis. A perturbation to these highly
coordinated cellular activities often results in bone metabolic and degenerative diseases such as osteoporosis.
Osteoporosis is a disease of dysregulated bone homeostasis characterized by low bone mass and a significant
increase in fracture risk. This pathological condition represents a major public health problem with
osteoporosis-associated fractures occurring in an estimated one in two women and one in four men age 50
and older in the United States alone. We recently showed adenosine A2B receptor (ADORA2B), a G-protein
coupled receptor on the cell membrane, plays an important role during osteogenic and osteoclastic
differentiation of MSCs and macrophages respectively. These findings along with our ongoing studies highlight
the potential of ADORA2B as a novel therapeutic target for the treatment of diseases characterized by low
bone mass such as osteoporosis. Unlike most of the currently available drugs that only slow down disease
progression but do not promote bone formation, activation of ADORA2B offers a therapy with dual function that
promotes osteoblast differentiation (bone formation) while inhibiting osteoclast activity (bone resorption). By
employing a number of in vitro and in vivo models, we will: (1) study the role of ADORA2B on osteoblast and
osteoclast differentiation and unearth the underlying intracellular signaling mechanism, (2) determine the
therapeutic potential of targeting ADORA2B to treat postmenopausal osteoporosis by using an ovariectomized
mouse model, and (3) establish humanized osteoporotic bone in animal models. Targeting ADORA2B to treat
bone loss is not limited to the study of osteoporosis but has broad applications that can be extended to
treatment of various bone metabolic diseases. The humanized bone tissue models could lead to new enabling
technologies for drug discovery and overcome species-specific discrepant findings in preclinical studies.

## Key facts

- **NIH application ID:** 9857547
- **Project number:** 5R01AR071552-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Shyni Varghese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,823
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857547

## Citation

> US National Institutes of Health, RePORTER application 9857547, Adenosine A2B Receptor in Bone Health and Osteoporosis (5R01AR071552-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857547. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*