Project Details

Description

Osteoarthritis (OA), characterised by articular cartilage loss and pathological ossification, affects almost 9 million people in the UK and is a major financial, social and healthcare burden.

It is estimated that more than 33% of the UK population aged over 45 have sought treatment for osteoarthritis. For this reason, osteoarthritis is a major financial, social and healthcare burden. Current osteoarthritis treatments are limited and largely consist of the use of pain-killers and physiotherapy. In some individuals, osteoarthritis progresses to the extent that total joint replacement is required. Currently we are unable to identify those at risk of developing osteoarthritis. We are also unable to treat those at early disease stages.

To change this, we must identify the genes, molecules and processes which cause osteoarthritis. Osteoarthritic joints, most often knees and hips, undergo structural deterioration, characterised by loss of the joint cartilage which covers the bone ends and normally allows pain-free joint movement. In joint cartilage, the resident cell type - the chondrocyte - needs to maintain a very stable, 'permanent' state so as to preserve and protect this tissue throughout life.

This is in stark contrast to the other main type of cartilage in the body (the growth cartilage), which is responsible for all bone growth and which strangely has almost opposite characteristics to the joint cartilage. In the growth cartilage, the chondrocytes are able to easily transition between different states to enable bone growth and therefore only ever have a 'temporary' state.

My previous research has shown that in a murine model of ageing-related OA, the articular cartilage chondrocytes undergo a transition from their inherently stable phenotype to a transient one, characteristic of the chondrocytes in the growth plate. Moreover, I revealed an association between growth abnormalities and OA development. This project will build upon this, to translate these pilot data to the human condition, and to examine the hypothesis that: Retaining a stable articular cartilage phenotype protects against OA

To deliver this, this project will answer:
1) Do altered growth dynamics underpin OA predisposition?
2) Can a switch to a transient chondrocyte phenotype contribute to OA?
3) Does targeted stabilisation of the chondrocyte phenotype protect against OA?

This project will examine why the switching between the two distinct types of chondrocytes ('permanent' vs. 'temporary') in the joint cartilage produces an unstable tissue prone to deterioration and osteoarthritis. It will also look to examine whether we can predict those at risk of osteoarthritis from any abnormalities in their growth cartilage. Together, this research will identify clear targets which could then in the future be investigated for patient benefit. This is vital if we are to reduce the economic and social impact of this disease.

If we improve our understanding of the mechanisms underpinning disease aetiology this will enable us to deliver new paradigms to identify those at risk of OA, and to deliver personalised interventions to treat patients with OA.

This will permit us to identify at risk individuals, and consider therapeutic approaches based on mechanistic understanding. This will likely lead to long-term patient benefit and societal impact, essential to reduce the burden of this
globally relevant disease.

Total awarded = £432k
StatusActive
Effective start/end date4/09/183/09/21

Funding

  • MRC