USING CELL AND HUMAN MODELS TO IDENTIFY MECHANICAL DRIVERS OF OSTEOARTHRITIS

Osteoarthritis affects 600 million globally, causing a substantial burden of pain and disability, with no disease modifying treatments. Whilst age is the main risk factor for osteoarthritis, abnormal joint loading resulting from joint injury, skeletal malalignment, certain occupations or sports, and obesity are also major risk factors. These ‘mechanical’ drivers of osteoarthritis offer an opportunity to identify new mechanisms underlying the onset of osteoarthritis that could facilitate earlier diagnosis and the development of new treatments to prevent joint destruction. Bone is highly responsive to mechanical load and is subject to early changes in animal models of post-traumatic osteoarthritis. At least 90% of all bone cells are osteocytes embedded throughout the mineralised bone matrix, that orchestrate bone formation and resorption in response to mechanical stimuli. We have established a human osteocyte cell model and used it to investigate whether molecular responses to mechanical and inflammatory stimuli could influence joint degeneration. We have also measured inflammatory and bone remodelling markers in synovial fluids from patients with knee osteoarthritis. Comparison between the cell model readouts, and those that correlate to predicted joint loading in osteoarthritic patients are starting to reveal potential mechanical drivers of osteoarthritic pathology and pain.