Fibrotic signaling in OA: the interaction of inflammatory mediators and biomechanical cues
Osteoarthritis (OA) has long been regarded as a non-inflammatory cartilage disease caused by "wear and tear". However it is increasingly apparent that a strong inflammatory component orchestrates OA initiation and progression. Cartilage in OA becomes fibrotic and eventually the underlying bone is exposed.
Effective treatment of OA-associated cartilage lesions requires targeting the pathways modulating cartilage cell (chondrocyte) behaviour in OA. Other repair strategies include implantation of cells grown on scaffolds that will incorporate into the lesion site or of scaffolds alone with properties that actively encourage repair through ingrowth of tissue-resident cells.
In collaboration with Philippa Hulley, Andrew Price, Andrew Carr, and Peter Taylor we aim to characterise the inflammatory mediator and fibrotic signalling signatures of cartilage and other joint tissues following injury and in early and late disease. The interaction of the inflammatory milieu with fibrotic (e.g. TGFβ, Wnt) signalling is being investigated as a mechanism driving OA pathogenesis.
To facilitate repair of tissue we are studying how small molecule inhibitors modulate generation of articular cartilage from mesenchymal stem cells and how they can regulate the fibrotic and inflammatory interactions in chondrocytes (collaboration with Udo Oppermann).
Furthermore cell behaviour is influenced by interaction with implantable repair scaffolds. We are exploiting this inherent cellular response to assess how specific scaffold characteristics (e.g fibre diameter) enhances cartilage generation and modulates the inflammatory and fibrotic interactions characteristic of OA.