# Gpr68 modulation of myofibroblast dynamics during tendon healing

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2024 · $203,280

## Abstract

Following injury, tendon heals via a fibrotic scar-mediated process. This fibrotic response impairs restoration of
tendon structure and function, and there are currently no pharmacological approaches in standard use to
enhance the healing process. While the overall cell environment during healing is dynamic and complex,
myofibroblasts are key regulators of the healing process. During tendon healing, tenocytes undergo
progressive activation and differentiation in to myofibroblasts. Myofibroblasts synthesize, contract and remodel
the new extracellular matrix that is required for restoring tissue integrity. However, resolution of physiological
healing requires clearance of myofibroblasts, either via apoptosis or reversion to a basal fibroblast/tenocyte
state. Tissue fibrosis, including fibrotic tendon healing results from myofibroblast persistence. Indeed, we have
previously shown that tendon scar tissue from both mouse and humans is enriched for myofibroblasts that take
on an anti-apoptotic profile. As such, understanding the mechanisms, and identifying therapeutic approaches
to modulate myofibroblast dynamics during healing would fill critical knowledge gaps. We and others have
recently demonstrated that expression of the proton-sensing G-protein coupled receptor Gpr68/Ogr1 is
decreased during tissue fibrosis. Moreover, small molecule activation of Gpr68 can modulate both
myofibroblast differentiation and reversion of lung fibroblasts. Thus, in this high-risk high-reward proposal we
will define the efficacy of pharmacological activation of Gpr68 to modulate tenocyte-myofibroblast dynamics
during fibrotic tendon healing. In addition, our preliminary data suggest that changes in macrophage-specific
Gpr68 expression during healing underpin several aspects of myofibroblast function. The on-going interaction
between macrophages and myofibroblast is an important regulator of both physiological and fibrotic wound
healing. Therefore, we will dissect the cell-type specifics functions of Gpr68 in modulating tendon healing, and
in responding to small molecule activation of Gpr68. Successful completion of these studies will provide
important fundamental information related to regulation of the cell environment during tendon healing, and will
establish a novel pharmacological approach to enhance the tendon healing process.

## Key facts

- **NIH application ID:** 10899098
- **Project number:** 1R21AR083217-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Robert Matthew Kottmann
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $203,280
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899098

## Citation

> US National Institutes of Health, RePORTER application 10899098, Gpr68 modulation of myofibroblast dynamics during tendon healing (1R21AR083217-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10899098. Licensed CC0.

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