Inflammation and fibrosis in diseases of orthopaedic soft tissues.
The aim of our group is to identify the mechanisms underpinning the development of chronic inflammation and subsequent fibrosis in diseases of orthopaedic soft tissues. The Carr lab has developed high definition ultrasound guided fine needle biopsy techniques in patients to enable these studies. Using repeated biopsies where some patients have resolution of symptoms and some have persistent pain provides a unique opportunity to investigate the cellular and molecular processes associated with both persistence and resolution of symptoms.
Our recent focus on tendon disease has identified inflammatory pathways activated in early and advanced stage disease, and characterised the phenotypes of immune cells and resident stromal fibroblasts in these tissues. We recently identified that functionally distinct tendons such as those in the shoulder and ankle share common cellular and molecular inflammatory mechanisms. Our work has also highlighted the mechanisms by which inflammation fails to resolve, and identified pathways implicated in the fibrotic repair of tendons after injury.
We are seeking to expand our disease mechanism programme to encompass other common diseases of orthopaedic soft tissues, including calcific tendinopathy and frozen shoulder (adhesive capsulitis). The cellular and molecular mechanisms active in these painful and debilitating conditions are yet to be elucidated. These projects will investigate if there are shared mechanisms of inflammation and fibrosis in these distinct patient cohorts and inform target discovery and therapeutic strategy for common diseases of orthopaedic soft tissues.
Molecular biology techniques are established in the group, and comprise tissue culture (primary cells), flow cytometry, cell viability assays, real time quantitative PCR, histology, immunohistochemical techniques. Other skill sets such as presentation and communication abilities, team working and multi-tasking are important parameters for success. New postdoctoral fellows will have the opportunity to participate in a departmental mentorship scheme to support their integration into the Department.
- S. G. Dakin, C. D. Buckley, M. H. Al-Mossawi, R. Hedley, F. O. Martinez, K. Wheway, B. Watkins, A. J. Carr, Persistent stromal fibroblast activation is present in chronic tendinopathy. Arthritis Res Ther Jan 25, (2017)
- S. G. Dakin, F. O. Martinez, C. Yapp, G. Wells, U. Oppermann, B. J. Dean, R. D. Smith, K.Wheway, B. Watkins, L. Roche, A. J. Carr, Inflammation activation and resolution in human tendon disease. Science translational medicine 7, 311ra173 (2015).
- Goodier HC, Carr AJ, Snelling SJ, Roche L, Watkins B, Dakin SG. (2016) Comparison of transforming growth factor beta expression in healthy and diseased human tendon. Arthritis res Ther. Feb 17; 18:48.
- Mosca, M, Carr AJ, Snelling SJ, Wheway K, Watkins B, Dakin SG. Differential expression of alarmins S100A9, IL33, HMGB1 and HIF1a in supraspinatus tendinopathy before and after treatment. Accepted, BMJ Open Sport Exerc Med.
- Morita W, Snelling SJ, Dakin SG, Carr AJ. (2016) Profibrotic mediators in tendon disease: a systematic review. Arthritis Res Ther. 2016 Nov 18;18(1):269.