Preclinical research

Altered joint biomechanics and joint injury are risk factors for osteoarthritis (OA).  However, the ways in which healthy mechanical load maintains joint homeostasis, and abnormal loads cause degeneration are unknown.

Our preclinical research programme aims to understand how mechanical loading leads to anabolic, catabolic, inflammatory and nociceptive signals in joint tissues, and contribute to symptoms, onset and progression of joint disease.

This will enable us to predict biological effects of altered joint biomechanics due to injury or surgery which in turn, will inform clinicians about timing and methods of surgery and/or rehabilitation. Since mechanically regulated signals in joint tissues directly influence inflammation, pain and pathology, they offer opportunities to prevent symptoms and disease. This research is identifying and investigating new drug targets to prevent progression of OA and new biomarkers that can predict arthritis onset and progression and indicate efficacy of surgical/rehabilitation/drug intervention.

Treatment options

There are no cures for OA and current treatments primarily focus on pain management. Since the substantial cost of OA to society is rapidly increasing with prolonged life spans and higher expectations of healthy, active ageing, new therapeutic options (drugs, surgery, rehabilitation, orthotics) are urgently required. Of current approaches, none directly target the effect of mechanical loading in disease progression and symptoms by using underlying biological mechanisms to define new treatment options. We are not aware of any that have translated such findings from basic science to human intervention trials. 

Through our research, we have:

• created in vitro and in vivo loading and arthritis models
• generated longitudinal data matching biomechanics to biology in arthritic humans, via effective collaboration between experts in orthopaedics, rehabilitation, engineering and basic science. 

This unique combination of expertise has revealed mechanically-regulated biological mechanisms with promising translational potential.

Our objectives

We aim to reveal biological mechanisms underlying mechanical loading that can be translated into interventions. The objectives are to:

• determine how biomechanical signals influence inflammation, pain and pathology
• identify mechanically-induced signals that initiate anabolic and catabolic responses
• identify mechanically-regulated biomarkers that change in arthritis.

Our key projects

Although we have various molecular targets at different stages of research development we have focused on key projects that illustrate our progress under each objective. These projects are:

• Glutamate drives inflammation, pain and pathology in arthritis.
• Mechanical mechanisms, biomarkers and interventions in vivo.
• Mechanical mechanisms, biomarkers and interventions in vitro.
• Biomarkers.