RhoA controls Wnt upregulation on microstructured titanium surfaces.

Lumetti, Simone; Mazzotta, Silvia; Ferrillo, Sara; Piergianni, Maddalena; Piemontese, Marilina; Passeri, Giovanni; Macaluso, Guido Maria; Galli, Carlo

Abstract

Rough topography enhances the activation of Wnt canonical signaling in vitro, and this mediates its effects on cell differentiation. However, the molecular mechanisms underlying topography-dependent control of Wnt signaling are still poorly understood. As the small GTPase RhoA controls cytoskeletal reorganization and actomyosin-induced tensional forces, we hypothesized that RhoA could affect the activation of Wnt signaling in cells on micropatterned titanium surfaces. G-LISA assay revealed that RhoA activation was higher in C2C12 cells on rough (SLA) surfaces under basal conditions than on smooth (Polished) titanium. Transfection with dominant negative RhoA decreased Wnt activation by normalized TCF-Luc activity on SLA, whilst transfection with constitutively active RhoA increased TCF-Luc activation on Polished titanium. One mM Myosin II inhibitor Blebbistatin increased RhoA activation but decreased Wnt activation on SLA surfaces, indicating that tension-generating structures are required for canonical Wnt modulation on titanium surfaces. Actin inhibitor Cytochalasin markedly enhanced RhoA and TCF-Luc activation on both surfaces and increased the expression of differentiation markers in murine osteoblastic MC3T3 cells. Taken together, these data show that RhoA is upregulated in cells on rough surfaces and it affects the activation of Wnt canonical signaling through Myosin II modulation.

Citation

LUMETTI, S., MAZZOTTA, S., FERRILLO, S., PIERGIANNI, M., PIEMONTESE, M., PASSERI, G., MACALUSO, G.M. and GALLI, C. 2014. RhoA controls Wnt upregulation on microstructured titanium surfaces. BioMed research international [online], 2014, article ID 401859. Available from: https://doi.org/10.1155/2014/401859

• Journal Article Type: Article
• Acceptance Date: Mar 20, 2014
• Online Publication Date: May 14, 2014
• Publication Date: Dec 31, 2014
• Deposit Date: Jul 29, 2024
• Publicly Available Date: Jul 29, 2024
• Journal: BioMed research international
• Print ISSN: 2314-6133
• Electronic ISSN: 2314-6141
• Publisher: Hindawi
• Peer Reviewed: Peer Reviewed
• Volume: 2014
• Article Number: 401859
• DOI: https://doi.org/10.1155/2014/401859
• Keywords: Wnt signalling; Cytoskeletal organization; Ras homolog family member A (RhoA)
• Public URL: https://rgu-repository.worktribe.com/output/2270436