# GP130/STAT3 signalling in articular cartilage development and regeneration

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $70,985

## Abstract

PROJECT SUMMARY
Articular cartilage is a highly specialized tissue that protects diarthrodial joints from forces associated with load
bearing, and allows nearly frictionless motion between articular surfaces. Articular cartilage injury often leads to
osteoarthritis (OA). OA currently affects more than 25 million people in the United States alone, making joint
surface restoration a major priority in modern medicine. The regenerative capacity of adult articular cartilage
has traditionally considered to be negligible, but several recent reports suggest that the regenerative potential
of articular cartilage may be underestimated. Based on our preliminary data, we hypothesize that signaling
through the Leukemia Inhibitory Factor Receptor-Glycoprotein 130/Janus Kinase/Signal Transducer and
Activator of Transcription 3 (LIFR/gp130/JAK/STAT3) pathway is essential during devleopment, and can
stimulate adult chondrocytes to assume a proliferative and migratory phenotype, similar to what occurs during
fetal joint development, thereby promotimg the maintenance of articular cartilage. Moreover, we identified a
novel small molecule termed Regulator of Cartilage Growth and Differentiation 423 (RCGD 423) that potently
and selectively agonizes this pathway in a gp130-dependent manner. We therefore test whether manipulation
of gp130-STAT3 signaling, both genetically or pharmacologically, can modulate the development and
progression of OA. First, the role of LIFR and STAT3 signaling in establishment and maintenance of mouse
cartilage during development will be defined. Next, we will test the consequences of gain and loss of STAT3
function in cartilage regeneration in a mouse injury model designed to mimic OA. The final set of experiments
will evaluate the effects of RCGD 423 and test the hypothesis that this molecule acts by modulating gp130
signaling in mouse cartilage repair and degeneration. The experiments in this proposal are anticipated to
define a novel function for LIFR-gp130/STAT3 signaling in cartilage establishment and repair, and to
demonstrate that manipulation of this pathway can prevent degeneration in mouse models of osteoarthritis. If
these experiments are successful, a critical new pathway regulating cartilage development, repair and
degeneration will have been identified. In addition, a small molecule agonist of gp130 signaling that can slow
the progression of articular cartilage degradation will be ready for pre-clinical testing and development.

## Key facts

- **NIH application ID:** 10440806
- **Project number:** 3R01AR071734-04S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** DENIS EVSEENKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,985
- **Award type:** 3
- **Project period:** 2018-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440806

## Citation

> US National Institutes of Health, RePORTER application 10440806, GP130/STAT3 signalling in articular cartilage development and regeneration (3R01AR071734-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440806. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*