# Research Supplements to Promote Re-Entry: Role of Glucose metabolism in Chondrocyte Mechanotransduction

> **NIH NIH R01** · MONTANA STATE UNIVERSITY - BOZEMAN · 2020 · $120,459

## Abstract

Project Summary
This re-entry supplement will support postdoctoral studies of Dr. Priyanka Brahmachary. All cells are
subject to and respond to mechanical forces like compression, and the aims of this project are (1) to
study glucose metabolism by chondrocytes in vivo and (2) to delineate the effects of a High Fat Diet on
synovial joint mechanotransduction in mice. However, the molecular mechanisms linking the mechanics
to biological responses are not fully understood. The cells of our model system, the chondrocytes of
articular cartilage, undergo compression in vivo, and these cells can transduce compression into
biological signals. There is evidence that glucose utilization in chondrocytes is regulated by compression
and that physiologic compression stimulates glycolysis, the currently accepted pathway chondrocytes
use to make ATP. This phenomenon has been linked to the ability of chondrocytes to maintain cartilage.
This project tests the hypothesis that physiological compression of both normal and osteoarthritic
chondrocytes results in a specific pattern of metabolites within glucose metabolism that support protein
production to maintain the cellular microenvironment. The premise is that by quantifying glucose
metabolism in chondrocytes these studies will advance strategies that use mechanical loading to produce
the building blocks for cartilage repair. Aim 1 - Experiments using mice subjected to voluntary running
will assess in vivo mechanotransduction. Dependent variables include sex and the duration of running.
Readouts will include both targeted metabolites and immunohistological markers examining regulation of
glucose metabolism. Assays will employ highly specific enzyme inhibitors that will allow a step-by-step
analysis of critical metabolic pathways. Aim 2 - Obesity is one of the important risk factors associated
with OA and is associated with chronic and systemic inflammation that precedes OA pathology. Studies
show that changes in blood metabolite levels, as a result of change in tissue and body composition also
play a role in the pathogenesis of OA. Experiments using mice fed a high fat diet and exposed to voluntary
exercise will help understand glucose metabolism in chondrocytes as well as the relation of
mechanotransduction to OA pathogenesis. Using a multidisciplinary approach involving specific
immunohistochemical markers and targeted metabolites, we will analyze the effects and underlying
molecular mechanisms of obesity related progression of OA and its effects on chondrocytes.
Understanding these mechanisms may prove useful in developing translational strategies to heal
cartilage by activating existing mechanosensitive pathways. Insight into how chondrocytes respond to
compression will advance osteoarthritis translation by providing new therapeutic targets for cartilage
repair and enabling substantial clinical progress.

## Key facts

- **NIH application ID:** 10086619
- **Project number:** 3R01AR073964-02S1
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** Ronald Kent June
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $120,459
- **Award type:** 3
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086619

## Citation

> US National Institutes of Health, RePORTER application 10086619, Research Supplements to Promote Re-Entry: Role of Glucose metabolism in Chondrocyte Mechanotransduction (3R01AR073964-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10086619. Licensed CC0.

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