# BCCMA: Cartilage Repair Strategies to Alleviate Arthritis Pain (Care AP): Targeting Pattern-Recognition to Reduce Pain-Related Pathology in Osteoarthritis

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2024 · —

## Abstract

Osteoarthritis (OA) is highly prevalent in U.S. military service members and Veterans due to the impact of joint
trauma and overuse injury. Its socioeconomic impact is substantial, estimated to approach $60 billion per year,
and no disease-modifying treatments exist. The overall goal of the collaborative Program is to develop a
treatment for post-traumatic osteoarthritis (PTOA) that will relieve pain and improve function. We hypothesize
that PTOA is caused by maladaptive repair responses including activation of the pro-inflammatory pathways of
innate immunity that in turn result in pain, loss of function and structural decline. This Program address the
hypothesis through two highly-integrated aims: (1) developing innovative non-pharmacologic and intra-articular
therapies inhibiting local pain and inflammation, and (2) optimizing mesenchymal stem cell (MSC)-based
therapies for reconstruction of the damaged joint.
The goal of this proposal is to develop novel therapy to diminish OA-associated pain by reducing inflammation
and bone remodeling through inhibition of the receptor CD14. We were the first to discover high levels of CD14
in OA patients, and others subsequently linked CD14 to pain in OA patients. CD14 is a pattern-recognition
receptor expressed by monocytes, macrophages and osteoclasts (bone-resorbing myeloid cells), that
augments innate immune responses to tissue injury, like that observed in the joint in PTOA. Our group has
now demonstrated that genetic deficiency of CD14 reduces pain and bone remodeling after joint injury in mice,
and prevents progression of arthritic cartilage damage. We hypothesize that CD14 receptor activation
promotes OA pain and pathology by enhancing inflammation and modifying osteoclast activity, and
anticipate that CD14 blockade can be developed as a therapeutic option to treat pain and inflammation
in OA. We will utilize in vitro techniques, small and large animal models of disease to understand how this
receptor can be effectively inhibited to reduce pain, inflammation and joint pathology. Specifically, in Aim 1 we
will use two complementary murine models of PTOA to determine how genetic deficiency of CD14 alters
patterns of pain, inflammation, and bone remodeling, and modifies osteoclast activity. We will use cell and
tissue culture along with imaging to identify the main cellular sources of CD14 in joint tissues. Finally, in Aim 2
we will test whether intra-articular inhibition of CD14 can reduce development of pain and progression of PTOA
in murine and porcine models of meniscal injury. This project will establish anti-CD14 therapy as safe and
effective in preclinical models of PTOA. As clinically-tested neutralizing anti-CD14 antibodies to interfere with
this pathway in humans are available, this will set the stage for translation to future clinical trials of this
approach in Veterans and others with OA.

## Key facts

- **NIH application ID:** 10871805
- **Project number:** 5I01BX004912-03
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Carla Rose Scanzello
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871805

## Citation

> US National Institutes of Health, RePORTER application 10871805, BCCMA: Cartilage Repair Strategies to Alleviate Arthritis Pain (Care AP): Targeting Pattern-Recognition to Reduce Pain-Related Pathology in Osteoarthritis (5I01BX004912-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871805. Licensed CC0.

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