Dakin Group | Soft Tissue Joint Disease
The Dakin Group undertakes translational research focusing on identifying the cellular and molecular basis of inflammatory fibrotic soft tissue joint diseases, with research programmes on tendinopathy, frozen shoulder and knee arthrofibrosis. Understanding the cellular and molecular basis of these diseases will inform new therapeutic approaches targeting tissue resident stromal cells of the joint, to promote resolution of inflammatory fibrotic disease.
- Identify the cellular & molecular basis of common soft tissue joint diseases
- Identify new therapeutic strategies to promote resolution of inflammatory soft tissue joint disease
We have developed access to well-phenotyped patient cohorts and refined biopsy procedures, providing a platform to investigate the cellular basis of tendon disease (tendinopathy). Our discoveries have catalysed a step change in understanding of how inflammation contributes to the development of chronic tendon disease, highlighting:
- Macrophages show complex activation states that change with disease stage
- Diseased tendon stromal cells show an activated pro-inflammatory phenotype and capacity for inflammation memory
- Diseased tendon stromal cells show dysregulated resolution responses
Tending towards resolution
Our studies reveal that tissue-resident stromal cells including macrophages and fibroblasts are pivotal populations driving chronic tendon inflammation. These cells represent untapped therapeutic targets in the treatment of tendinopathy. Resolution pharmacology provides a new therapeutic approach to harness the capacity of proresolving lipid mediators and their receptors to drive chronic tendon inflammation towards a resolving pathway.
Frozen shoulder is a chronic inflammatory fibrotic disease affecting the shoulder joint capsule causing significant pain and restricted shoulder joint motion. The condition is unique in that it almost always spontaneously resolves over time. This programme will investigate the cellular basis underpinning how inflammatory fibrosis in this condition ultimately resolves over time. The findings will advance healthcare via identification of effective new therapies to (1) accelerate resolution of frozen shoulder and (2) jump start other chronic inflammatory fibrotic joint diseases down a resolving pathway.
To learn more about our ICECAP clinical study investigating advanced-stage Frozen Shoulder click here.
To learn more about our FreeCAP clinical study investigating early-stage frozen shoulder click here.
Arthrofibrosis is the pathologic stiffening of a joint due to an exaggerated inflammatory fibrotic response leading to the development of non-compliant scar tissue. As a common complication following total knee arthroplasty, knee arthrofibrosis is a significant cause of pain and disability for patients, with up to 25% of patients requiring additional surgery to restore adequate knee joint motion. This programme will identify the cellular and molecular basis underpinning why fibrosis in the knee joint persists in contrast to the shoulder joint where fibrosis ultimately resolves. Findings from this research will identify new therapeutic strategies to promote resolution of knee arthrofibrosis, reducing the requirement for patients to undergo repeated surgery.