# Modulation of Inflammation in Osteoarthritis via CD14-mediated pattern recognition

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $493,888

## Abstract

ABSTRACT
Osteoarthritis (OA) is a leading cause of disability in adults, causing chronic progressive joint pain and tissue
damage throughout the joint. No current medical treatments are effective at preventing the progressive joint
deterioration, pain and disability characteristic of OA. Although it is known that inflammation and bone-
remodeling are major drivers of OA pain and pathology, it is not yet clear which molecular pathways directly
drive chronic OA pain and disease progression or are key targets for therapeutic development. Our lab has
shown that deficiency of CD14, an inflammatory pattern-recognition receptor expressed by macrophages and
other myeloid cell types, protects against OA-associated bone-remodeling and pain-related joint dysfunction
after knee injury in mice. In patients, CD14 is increased in joint fluid and associated with intra-articular
macrophage infiltration as well as pain severity. This receptor facilitates Toll-like receptor (TLR) signaling.
TLRs are innate immune sensors which are important initial triggers of chronic inflammation in response to
non-infectious tissue damage. In addition, our team has recently demonstrated that TLR-signaling is critical to
development of knee OA pain in mice, via direct stimulation of pain-transmitting (nociceptive) neurons in the
dorsal root ganglia (DRG) that innervate the knee. In this proposal, we will test the hypothesis that CD14 on
myeloid cells including macrophages promotes OA pain-related pathology (bone remodelling and
inflammation), while CD14 also augments OA pain by directly sensitizing neurons innervating the
arthritic joint. We will utilize in vitro techniques and the murine destabilization of the medial meniscus (DMM)
model of OA, to understand the cellular and molecular mechanisms by which CD14 drives OA pathology and
inflammation in joint tissues. Specifically, in Aim 1 we will use a multi-disciplinary approach to determine how
genetic deficiency of CD14 modifies inflammation and bone-remodeling during progression of OA, using the
DMM model. We will determine the contribution of myeloid cells to inflammation and bone-remodeling in the
model by using bone marrow (BM) chimeric mice. Lastly, we will test the effects of CD14 on differentiation of
cells that drive bone-remodeling (osteoclasts) and production of inflammatory mediators of pain from myeloid
cell types. In Aim 2 we will characterize effects of CD14 on TLR-mediated DRG neuronal activation and joint
pain. We will use TLR stimuli with relevance to OA to evaluate DRG responses in vitro, comparing WT and
CD14-deficient cells. We will additionally compare pain responses to injection of TLR-stimuli into the joint, and
expect that both DRG responses and pain will be blunted in the CD14 deficient strain. Finally, in Aim 3 we will
test whether pharmacological targeting of CD14 reduces OA progression and pain after DMM-induced injury.
This study will then specify the molecular and cellular framework to design future ...

## Key facts

- **NIH application ID:** 10052718
- **Project number:** 1R01AR075737-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Carla Rose Scanzello
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $493,888
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052718

## Citation

> US National Institutes of Health, RePORTER application 10052718, Modulation of Inflammation in Osteoarthritis via CD14-mediated pattern recognition (1R01AR075737-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10052718. Licensed CC0.

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