# Intraarticular microbial DNA as a novel mediator of osteoarthritis

> **NIH NIH R61** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $437,000

## Abstract

Project Summary / Abstract
The objective of the proposed research is to better understand how cartilage microbial DNA patterns are
established, and how these relate to osteoarthritis (OA) pathogenesis and progression. Previously published
studies have outlined both gut microbiome pro-inflammatory changes with aging generally, but no work has yet
been performed to examine how the gut and/or cartilage microbiomes, inflammation, and epigenetics intersect
with OA. Our laboratory has previously examined in detail the epigenetic changes within cartilage and
subchondral bone that are associated with OA development, and we have recently examined epigenetic changes
within peripheral blood cells of human OA patients which are associated with increased risk of rapid OA
progression. Our first Aim is to determine whether the cartilage microbial DNA pattern originates from the
gut microbiome. To do this, we will populate the gut microbiome of germ-free mice with microbiota from young
and OA-susceptible C57BL6/J (B6) mice then determine cartilage microbial DNA patterns at prespecified
timepoints following inoculation. If successful, we will go on to test how variations in the cecal microbiome,
associated with OA risk factors including aging and obesity, are reflected in changes of the cartilage microbiome
profile. Furthermore, we will determine whether already-established cartilage microbiome patterns can be
altered via changing the gut microbiome. Our second Aim will determine whether cartilage microbial DNA is
sufficient to change the risk for OA development in mice. To do this, we will inject microbial DNA amplified from
human OA patients and healthy controls into the knee joints of germ-free mice, then induce OA by disruption of
the medial meniscus (DMM) surgery and measure histopathological outcome. If successful, we will then go on
to determine local and systemic inflammatory cell population changes by CyTOF, serum cytokine changes by
Bioplex assay, and epigenetic and transcriptomic changes on a genome-wide level following intraarticular
microbial DNA delivery. The proposed work is important, as we do not have a full understanding of how
non-genetic OA risk factors increases OA risk, nor do we understand how the microbiome influences OA risk.
Our work is quite innovative in its use of germ-free mouse microbiome transplantation to evaluate OA and
the use of cutting-edge CyTOF and epigenetic analyses. Finally, we will be the first to evaluate whether gut
microbiome transplantation may be used as a therapeutic agent to prevent OA. Success in our proposal may open
a new avenue for OA aging research and may offer a novel treatment strategy for OA.

## Key facts

- **NIH application ID:** 10083042
- **Project number:** 1R61AR078075-01
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Matlock Jeffries
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,000
- **Award type:** 1
- **Project period:** 2020-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083042

## Citation

> US National Institutes of Health, RePORTER application 10083042, Intraarticular microbial DNA as a novel mediator of osteoarthritis (1R61AR078075-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10083042. Licensed CC0.

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