RAC1 AND RHOA-ROCK REGULATION OF OSTEOBLAST DIFFERENTIATION ON ROUGH AND SMOOTH TITANIUM SURFACES

Modulation of surface topography is an effective way to control cellular response and enhance osseointegration of implants; however it is unclear how surface topography influences osteoblasts at the molecular level. One of the most frequently observed changes in cellular behaviour is the organization of the cytoskeleton and actin polymerization which is regulated by the Rho-family of GTPases. We hypothesized that these GTPases (specifically Racl and RhoA), play a role in osteoblast response to surface topography and affect differentiation and mineralization. Osteoconductive rough topographies and non- osteoconductive smooth topographies were used as models to elucidate the roles of Racl and RhoA. Rat-calvaria derived osteoblasts cultured under Racl inhibition significantly decreased migration and differentiation and mineralization on rough surfaces. RhoA-protein associated kinase (ROCK)-inhibition resulted in decreased adhesion formation, and increased differentiation and mineralization on both surfaces, but did not affect migration. This study shows that the addition of RhoA-ROCK inhibitors to culture media accelerates osteoblast differentiation and mineralization in vitro and may represent a new therapeutic to accelerate healing around implants in vivo