The Role of Integrin alpha1beta1 and Epidermal Growth Factor Receptor Signalling in Post-traumatic Osteoarthritis

Abstract

Purpose: The purpose of this thesis was to investigate the role of integrin α1β1 in the progression of post-traumatic osteoarthritis (PTOA), and epidermal growth factor receptor (EGFR) signalling as the mechanism(s) by which integrin α1β1 might delay signs of PTOA. Methods: Surgery to destabilise the medial meniscus was performed on integrin α1-null and wildtype mice and the progression of PTOA was monitored for 12 weeks using microCT, histology, and behavioural testing. The EGFR-inhibitor erlotinib was administered to a subset of mice. Results: Cartilage damage occurred four weeks earlier in α1-null compared to WT female mice. Independent of genotype, cartilage damage and bony signs of PTOA were lessened by erlotinib treatment in female mice. Conclusion: Integrin α1β1 protects against PTOA-induced cartilage degradation up to 8 weeks post-surgery partially via the dampening of EGFR signalling, in female mice. Furthermore, EGFR signalling aggravates the development of PTOA in female but not male mice.