Pharmacological GSK-3beta inhibition improves osteoblast differentiation on titanium surfaces.

Rough titanium surfaces enhance the activation of Wnt canonical signaling, a pathway required for osteoblast differentiation. The present study investigated the effects of GSK3b-inhibitor (2’Z,3’E)- hydrophilic SLA titanium discs (modSLA) and stimulated with increasing doses of BIO. Activation of same cell system by Real Time PCR. Osteoblastic MC3T3 cells were then plated on discs with or without activated Wnt canonical signaling in C2C12 cells on all surfaces, and the highest effect was on rough rough surfaces at the concentration of 100 nM, and on all surfaces at the concentration of 1 mM. BIO be a viable approach to improve cell response to implant surfaces

RhoA Controls Wnt Upregulation on Microstructured Titanium Surfaces.

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

Treatment of macular edema because of occlusive vasculitis with bevacizumab (avastin): efficacy of three consecutive monthly injections.

PURPOSE: To report the efficacy of intravitreal bevacizumab, administered in a series of three monthly injections followed by a period of observation, in the treatment of cystoid macular edema because of occlusive vasculitis. METHODS: This is a retrospective review of 13 consecutive eyes of 13 patients with cystoid macular edema because of occlusive vasculitis, which had been unresponsive to other medications and were treated with intravitreal bevacizumab (1.25 mg). The evaluation consisted of a complete ophthalmologic examination, including best-corrected visual acuity measurement, ophthalmoscopy, fluorescein angiography, and optical coherence tomography. The eyes received a series of 3 monthly injections followed by a 3-month observation period. RESULTS: A significant improvement in foveal thickness and visual acuity was obtained after the first injection, which increased after the second and the third injections and was maintained for 1.5 months after the last injection. The 2 parameters returned to the baseline values 3 months after the last treatment. There were no ocular or systemic adverse effects. CONCLUSION: Intravitreal injection of bevacizumab seems to be well tolerated and is associated with short-term improvement of visual acuity and decreased retinal thickness in patients with cystoid macular edema because of vasculitis that is resistant to conventional