ABSTRACT
Abstract Objective The present study aimed to investigate the participation of focal adhesion kinases (FAK) in interactions between osteoblastic cells and titanium (Ti) surfaces with three different topographies, namely, untreated (US), microstructured (MS), and nanostructured (NS). Methodology Osteoblasts harvested from the calvarial bones of 3-day-old rats were cultured on US, MS and NS discs in the presence of PF-573228 (FAK inhibitor) to evaluate osteoblastic differentiation. After 24 h, we evaluated osteoblast morphology and vinculin expression, and on day 10, the following parameters: gene expression of osteoblastic markers and integrin signaling components, FAK protein expression and alkaline phosphatase (ALP) activity. A smooth surface, porosities at the microscale level, and nanocavities were observed in US, MS, and NS, respectively. Results FAK inhibition decreased the number of filopodia in cells grown on US and MS compared with that in NS. FAK inhibition decreased the gene expression of Alp, bone sialoprotein, osteocalcin, and ALP activity in cells grown on all evaluated surfaces. FAK inhibition did not affect the gene expression of Fak, integrin alpha 1 ( Itga1 ) and integrin beta 1 ( Itgb1 ) in cells grown on MS, increased the gene expression of Fak in cells grown on NS, and increased the gene expression of Itga1 and Itgb1 in cells grown on US and NS. Moreover, FAK protein expression decreased in cells cultured on US but increased in cells cultured on MS and NS after FAK inhibition; no difference in the expression of vinculin was observed among cells grown on all surfaces. Conclusions Our data demonstrate the relevance of FAK in the interactions between osteoblastic cells and Ti surfaces regardless of surface topography. Nanotopography positively regulated FAK expression and integrin signaling pathway components during osteoblast differentiation. In this context, the development of Ti surfaces with the ability to upregulate FAK activity could positively impact the process of implant osseointegration.
Subject(s)
Animals , Osteoblasts/drug effects , Sulfones/pharmacology , Titanium/chemistry , Quinolones/pharmacology , Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors , Osteoblasts/physiology , Sulfones/chemistry , Surface Properties , Microscopy, Electron, Scanning , Signal Transduction , Gene Expression , Integrins/analysis , Cell Differentiation/drug effects , Cells, Cultured , Osseointegration/drug effects , Rats, Wistar , Quinolones/chemistry , Cell Proliferation/drug effects , Focal Adhesion Protein-Tyrosine Kinases/analysis , Focal Adhesion Protein-Tyrosine Kinases/chemistry , Real-Time Polymerase Chain ReactionABSTRACT
Considering importance of developing selective COX-2 inhibitors, COX-2 binding affinity data of 4-(2-aryl-1-imidazolyl)-phenyl methyl sulfones and sulfonamides (n = 83) have been modeled using electrotopological state (E-state) index as electronic parameter, hydrophobic substituent constant (pi) and molar refractivity (MR) of aryl ring substituents as lipophilic and steric parameters, respectively. Additionally, suitable dummy parameters have been used for the development of multiple regression equations in a stepwise manner. The study suggests that lipophilicity of ortho, meta and para substituents of the aryl ring increases the binding affinity, while molar refractivity (MR) of ortho and meta substituents of the aryl ring decreases the binding affinity. Again, electron-withdrawing substituents at meta and para positions of the aryl ring increase the binding affinity. Additionally, a 4-fluoro substituent on the aryl ring, a trifluoromethyl substituent at R position and simultaneous presence of 3-chloro and 4-methyl groups on the aryl ring are conducive to the binding affinity. Also, an amino substituent is preferred over a methyl group at R2 position suggesting preference of the sulfonamide moiety over the methyl sulfone moiety for the COX-2 binding affinity. Furthermore, importance of E-state values of different atoms in the generated relations suggests the influence of electron density distribution over the 1,2-diarylimidazole nucleus for the binding affinity. For this data set, E-state parameters perform better as electronic parameters in comparison to Hammett sigma parameters. When lipophilic whole molecular descriptor (ClogP) is used, instead of hydrophobic substituent constant (pi), the former performs better than the latter.
Subject(s)
Animals , Chemistry, Physical/methods , Cyclooxygenase 2 Inhibitors/pharmacology , Electronics , Electrons , Humans , Imidazoles/chemistry , Models, Chemical , Molecular Structure , Multivariate Analysis , Quantitative Structure-Activity Relationship , Regression Analysis , Software , Sulfonamides/chemistry , Sulfones/chemistryABSTRACT
Aqueous sodium hydroxide reacts with [[[4-nitrogphenyl] methyl] sulphonyl]]-acetic acid [1] to give 4, 4[']-diformylazoxy-benzene and 4, 4[']--dicarboxyazoxybenzene as the main products, while in 50 percent water-dioxane medium the products are 4, 4[']--dihydroxmyethylazoxybenzene, 4, 4[']--dicarboxyazoxybenzene besides 4-carboxy, 4[']--hydroxymethylazoxybenzene and its isomer. 4-Nitrosobenzaldehyde is an intermediate in this reaction which via a Cannizzaro reaction gives the reaction products. Other 2-, 3-and 4-nitrobenzyl sulphones are studied