# The Role of Hyaluronan Interactions with CD44 and RHAMM in Cartilage Repair

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $223,740

## Abstract

Project Summary/Abstract
The repair of cartilage injuries still remains a major challenge. Despite the advancement of surgical techniques,
including microfracture surgery and cell-based approaches, all of these approaches do not form hyaline
cartilage but rather `hyaline-like' cartilage or fibrocartilage. Since the function of articular cartilage is linked to its
structure, all current surgical interventions to repair cartilage defects result in some impairment and the
development of post-traumatic osteoarthritis (PTOA). Therefore the development of novel therapeutic
strategies for cartilage repair is highly warranted. Our preliminary data suggest that hyaluronan (HA), a major
component of the cartilage extracellular matrix (ECM) together with a RHAMM-mimetic, HA-binding peptide
(P15-1) play a major role in the settlement of mesenchymal stem cells (MSCs) at the cartilage repair site and
their chondrogenic differentiation. This peptide inhibits the interaction of HA with one of its receptors, receptor
for hyaluronan-mediated motility (RHAMM). RHAMM associates with another HA receptor CD44. P15-1
prevents the interaction between HA and RHAMM and allows the clustering of CD44 by HA. Our collaborators
who discovered P15-1 have shown that HA/RHAMM/CD44 interactions stimulate stem cell migration and
proliferation but also fibrotic processes, including fibrotic tissue healing, whereas interfering with HA/RHAMM
interactions with P15-1 promoted a form of scarless skin wound healing. Our preliminary findings showing a
markedly improved cartilage repair of full thickness cartilage defect in rabbits after microfracture surgery and
three intra-articular injections of P15-1 together with high molecular weight (HMW)HA compared to intra-
articular injections of HMWHA alone, and a markedly improved attachment of bone marrow-derived
mesenchymal stem cells (BMSCs) to tissue culture plates coated with HMWHA and P15-1 compared to plates
coated with HMWHA only support our hypothesis that interfering with HA/RHAMM interactions in MSCs will
enhance settlement of these cells at the repair site and their chondrogenic differentiation leading to
enhanced cartilage repair. To test this hypothesis we propose two Aims. In Aim 1 we will perform in vitro
experiments using P15-1, antibodies that block HA/RHAMM and/or HA/CD44 interactions, RHAMM knockout (-
/-) BMSCs, and CD44-/- BMSCs to determine how the interactions of HA with RHAMM and CD44 affect BMSC
proliferation, migration, attachment to HA and chondrogenic differentiation. In Aim 2 we will confirm our in vitro
results and determine whether interfering with HA/RHAMM interactions via intra-articular injections of P15-1
together with HMWHA and BMSCs will lead to enhanced settlement of BMSCs at the repair site and improved
formation of hyaline cartilage. Finally, we will determine whether injections of BMSCs together with P15-1 and
HMWHA are more effective in cartilage repair than microfracture surgery and intra-articular inj...

## Key facts

- **NIH application ID:** 9872854
- **Project number:** 1R21AR076604-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** THORSTEN KIRSCH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $223,740
- **Award type:** 1
- **Project period:** 2020-02-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872854

## Citation

> US National Institutes of Health, RePORTER application 9872854, The Role of Hyaluronan Interactions with CD44 and RHAMM in Cartilage Repair (1R21AR076604-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872854. Licensed CC0.

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