Insights into musculoskeletal disease
Research aims to elucidate the developmental cascade of the osteoblast and chondrocyte lineages, both from known precursors and novel sources, and to explore their role in disease. Understanding how local niches impinge on the developmental cascade will provide insight into both the mechanisms underlying disease and the failure for these tissues to normally repair. Ongoing work has provided new insights into the location and form of sclerostin (Hernadez et al 2014) and studies linking the Departments of Chemistry and Surgery are using nuclear magnetic resonance spectroscopy to investigate chemical signatures within bone matrix and between the matrix and mineral phases of bone, discovering that poly(ADP ribose) (PAR) plays a role in the mineralisation process itself (Chow et al 2014).
Supporting musculoskeletal repair and replacement
Biomaterials and implantable devices are often used to replace or reinstate tissue or organ function lost through disease or injury. Key to the long term success of these approaches is the interaction between host and implanted material. If the biological interface between implant and host doesn’t favour repair then the outcome is poor. Therefore design of new biomaterials that consider cellular responses will improve tissue integration and ensure enhanced functional lifespan of the implant. Cell behaviour on biomaterials is dictated by a combination of absorbed biomolecules and surface topography. Research in the Department of Surgery uses several different approaches to understand the influence of these factors on cell adhesion, proliferation and differentiation with previous studies identifying how surface topography influences cell:cell communication (Kirmizidis et al 2009) and deposition of a mineralised matrix (Birch et al 2013). Building on these studies, as part of the Arthritis Research UK Tissue Engineering Centre.
Translating novel interventions and therapy for the clinic
Osteoarthritis (OA) is a significant healthcare burden and preventing or slowing its onset would alleviate considerable patient disability and suffering. One treatment approach is to enhance the surgically induced healing process with biomolecules such as fibroblast growth factor-18 (Barr et al 2014). Alternatively the use of cell therapies offers an exciting opportunity to treat early stage osteochondral lesions that otherwise would go on to initiate osteoarthritic changes. Cells, including stem cells, can be considered a target for treatment (resident) or a part of the therapy. For both strategies, our main approach is to consider cell and stem cell populations in the adult patient. For example recent studies have illustrated how peripheral blood derived cells can influence the motility and activity of both mesenchymal stem cells and chondrocytes (Hopper et al 2015 Nature Reviews- Rheumatology ). Responsible translation includes clinical trials and currently, we are looking, in a multicentre study, at the role of a cell therapy in avascular necrosis with Bonetherapeutics.
Understanding the success of these treatment approaches in patients is dependent upon being able to visualise and monitor bone and cartilage structure and organisation in fine detail. Researchers from the Department of Engineering and the Department of Medicine have developed novel imaging analysis technology for quantitative in vivo assessment of bone in 3D using computed tomography (Treece & Gee 2015). Initially applied for monitoring response to new anti-resorptive therapies in osteoporosis (Poole et al. 2014), these techniques have also been developed for the assessment of peri-articular bone in osteoarthritis (Turmezei et al. 2015*) and the quantification joint space, cartilage thickness and other relevant molecular imaging parameters from a cross-modality imaging platform (CT and MRI).
*Turmezei TD, Fotiadou A, Treece GM, Gee AH, Poole KES. (2015) Quantitative 3D analysis of bone in hip osteoarthritis using clinical computed tomography. European Radiology (in press).