# Girk2/3 channels in cartilage biology and disease

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $174,900

## Abstract

ABSTRACT
Long bones are formed and repaired through the process of endochondral ossification. Our goal is to
understand molecular mechanisms of endochondral bone growth and apply that knowledge to improve
musculoskeletal tissue regeneration and healing. Towards this goal, we made the novel discovery that
chondrocyte- and osteoblast-lineage cells express ion channels called GIRKs that control potassium transport
across cell membranes and activate intracellular programs after activation of G-protein-coupled receptors. We
demonstrate that GIRK subunits are expressed in chondrocyte- and osteoblast-lineage cells, but not
osteoclasts. Animals lacking both Girk2 and Girk3 have remarkably longer and denser bones, suggesting
greater cartilage and bone formation when Girk2 and Girk3 are absent or inactivated. The central hypothesis of
this project is that Girk2 and Girk3 cooperate to regulate chondrocyte and osteoblast survival, proliferation
and/or maturation during endochondral bone development. Our specific aims are to: 1) determine how Girk2
and Girk3 regulate growth plate chondrocyte maturation, 2) define how Girk2 and Girk3 contribute to
osteoblast-lineage maturation and bone density, and 3) determine if channels formed by Girk2 and Girk3 are
required for opioid-induced responses in chondrocytes and osteoblasts. The significance of this work is that
Girk2 and Girk3 are potentially druggable targets whose activities and/or expression could be controlled to
accelerate long bone growth and healing.

## Key facts

- **NIH application ID:** 9902333
- **Project number:** 5R21AR074228-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Jennifer J Westendorf
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,900
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902333

## Citation

> US National Institutes of Health, RePORTER application 9902333, Girk2/3 channels in cartilage biology and disease (5R21AR074228-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9902333. Licensed CC0.

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