Model of the mechanism of action in wild-type mice (Itga5+/+; Nisch+/+), during the onset OM in edison mice (Itga5+/+; Nischedsn/edsn) and in double mutants (Itga5tm1Hyn/+; Nischedsn/edsn). Nisch, Nischarin; Nischedsn, Nischarin with the edison mutation; ITGA5, integrin α5; ITGB1, integrin β1; FAK, Focal adhesion kinase; PAK1, p21-activated kinase 1; LIMK1, LIM domain kinase 1; Rac1, Ras-related C3 botulinum toxin substrate 1; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; SRC, Proto-oncogene tyrosine-protein kinase; VEGF, Vascular endothelial growth factor. Red capped lines represent inhibition, yellow capped lines represent reduced inhibition and grey capped lines represent low inhibition. The blue arrow indicates the role of ITGA5 in enhancing binding of NISCH to PAK1. Green arrows indicate direct activation of downstream members of the pathway and dashed green arrows indicate indirect activation. Grey arrows indicate slightly raised levels of proteins, while yellow indicates raised levels and red indicates highly raised levels.