Identifying a new treatment strategy for osteoarthritis: targeting the body’s response to injury

Disease - Osteoarthritis

Lead applicant - Dr Heba Ismail

Organisation - University of Sheffield

Type of grant - Career Development Fellowship

Status of grant - Active

Amount of the original award - £513,262.01

Start date - 1 November 2018

Reference - 22048

Public Summary

What are the aims of this research?

A major injury or operation on a joint may lead to osteoarthritis in that joint later in life. It has been found that injury to joint cartilage rapidly activates inflammatory responses. It is thought that these very early events following injury could be responsible for chronic ongoing inflammation. The aim of this research is to identify the key enzymes involved in controlling these inflammatory responses caused by injury, in order to find a specific pathway for targeting for development of new treatments.

Why is this research important?

Osteoarthritis is a disease that can be caused by injury, and currently there is no treatment available that is able to reverse the disease. As explained above, tissue injury activates within seconds through a number of cellular events that cause chronic inflammation, and in turn amplifies tissue damage. It is still unknown how cells sense injury and by what mechanism the tissue damage is driven.

Previous studies showed that activation of inflammatory pathways is caused by a series of protein modifications called ubiquitination. Identifying the key enzymes involved in these protein modifications in response to injury is crucial for understanding diseases caused by injury, such as osteoarthritis, and for designing new treatments based on potential new understanding.

How will the findings benefit people with arthritis?

The outcome of this research will lead to identifying the key enzymes involved in controlling inflammatory responses to injury, and therefore identifying them as potential targets in osteoarthritis for developing new treatments. As such, inhibitors of these enzymes are being developed for clinical use, specifically blocking the inflammatory amplification of tissue injury signals would be an important new avenue in developing new treatments for osteoarthritis.