Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay

Background: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans.Methods: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice.Results: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience.Conclusions: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy. © 2014 Weber et al.; licensee BioMed Central Ltd

TNF alpha contributes for attenuating both Y(397)FAK and Y(416)Src phosphorylations in osteoblasts

ObjectiveOur poor understanding of how inflammatory mediators can affect osteoblast behavior led us to investigate the tumor necrosis factor (TNF)-induced focal adhesion kinase (FAK) and Src phosphorylation. Material and MethodsMC3T3-E1 pre-osteoblast cells were harvested at specific time points after either TNF treatment or RAW267 stimulated conditioned medium, and thereafter cell extracts were prepared for Immunoblotting assay. ELISA detected TNF content at conditioned medium. Tumor necrosis factor--neutralizing antibodies also were used. ResultsIt was possible to show that TNF provokes attenuation at Y-phosphorylation of both FAK (at Y-397) and Src (at Y-416) proteins (P<0.05), suggesting a decrease in their activities. The very similar profile was observed when osteoblasts were incubated with conditioned medium from lipopolysaccharide (LPS)-stimulated macrophages, it being significantly different than control (FAK and Src, P<0.05). Nevertheless, in order to validate these findings, we decided to pre-incubate osteoblasts with anti-TNF neutralizing antibody (2gml(-1)) prior exposing to conditioned medium. Importantly, our results revealed that there was a diminution on those conditioned medium effects when the same biological parameters were evaluated (P<0.05). Moreover, we also showed that TNF impairs osteoblast adhesion, suggesting an interesting role on osteoblast performance. ConclusionsAltogether, these results suggest that LPS-stimulated macrophage mediators attenuate both FAK and Src activations in osteoblast, suggesting a novel role for TNF on osteoblast performance