Melatonin protects gingival mesenchymal stem cells and promotes differentiation into osteoblasts.

Melatonin (MEL) has antioxidant properties and participates in osteogenic differentiation. In periodontitis, in which increased oxidative stress and bone resorption are involved, mesenchymal stem cells derived from the gingiva (GMSCs) combined with MEL could be relevant for osteogenic regeneration. In this study, we studied the antioxidant and differentiating effect of MEL on an in vitro system of GMSCs. Primary culture of GMSCs from Wistar rats was developed to evaluate differentiation into osteoblasts with an appropriate medium with or without MEL. Marker genes of mesenchymal stem cells by real time-polymerase chain reaction, clonogenic capacity, and cell migration after wound assay were used to characterize GMSCs as mesenchymal stem cells. Alkaline phosphatase activity and the alizarin red technique were used to evaluate osteogenic activity and differentiation. MEL increased alkaline phosphatase activity and alizarin red values, promoting osteogenic differentiation. Besides this, MEL protected GMSCs in a model of cellular damage related to oxidative stress, returning viability to baseline. MEL was more effective in promoting and protecting GMSCs by the production of osteogenic cells when oxidative stress is present. This evidence supports the use of MEL as a novel bone-regenerative therapy in periodontal diseases.

Intestinal Ca2+ absorption revisited: A molecular and clinical approach.

Ca2+ has an important role in the maintenance of the skeleton and is involved in the main physiological processes. Its homeostasis is controlled by the intestine, kidney, bone and parathyroid glands. The intestinal Ca2+ absorption occurs mainly via the paracellular and the transcellular pathways. The proteins involved in both ways are regulated by calcitriol and other hormones as well as dietary factors. Fibroblast growth factor 23 (FGF-23) is a strong antagonist of vitamin D action. Part of the intestinal Ca2+ movement seems to be vitamin D independent. Intestinal Ca2+ absorption changes according to different physiological conditions. It is promoted under high Ca2+ demands such as growth, pregnancy, lactation, dietary Ca2+ deficiency and high physical activity. In contrast, the intestinal Ca2+ transport decreases with aging. Oxidative stress inhibits the intestinal Ca2+ absorption whereas the antioxidants counteract the effects of prooxidants leading to the normalization of this physiological process. Several pathologies such as celiac disease, inflammatory bowel diseases, Turner syndrome and others occur with inhibition of intestinal Ca2+ absorption, some hypercalciurias show Ca2+ hyperabsorption, most of these alterations are related to the vitamin D endocrine system. Further research work should be accomplished in order not only to know more molecular details but also to detect possible therapeutic targets to ameliorate or avoid the consequences of altered intestinal Ca2+ absorption.

Sodium deoxycholate inhibits chick duodenal calcium absorption through oxidative stress and apoptosis.

High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the effect of a single high concentration of NaDOC on the intestinal Ca(2+) absorption and the underlying mechanisms. Chicks were divided into two groups: 1) controls and 2) treated with different concentrations of NaDOC in the duodenal loop for variable times. Intestinal Ca(2+) absorption was measured as well as the gene and protein expressions of molecules involved in the Ca(2+) transcellular pathway. NaDOC inhibited the intestinal Ca(2+) absorption, which was concentration dependent. Ca(2+)-ATPase mRNA decreased by the bile salt and the same occurred with the protein expression of Ca(2+)-ATPase, calbindin D(28k) and Na(+)/Ca(2+) exchanger. NaDOC produced oxidative stress as judged by ROS generation, mitochondrial swelling and glutathione depletion. Furthermore, the antioxidant quercetin blocked the inhibitory effect of NaDOC on the intestinal Ca(2+) absorption. Apoptosis was also triggered by the bile salt, as indicated by the TUNEL staining and the cytochrome c release from the mitochondria. As a compensatory mechanism, enzyme activities of the antioxidant system were all increased. In conclusion, a single high concentration of NaDOC inhibits intestinal Ca(2+) absorption through downregulation of proteins involved in the transcellular pathway, as a consequence of oxidative stress and mitochondria mediated apoptosis.

Minireview on regulation of intestinal calcium absorption. Emphasis on molecular mechanisms of transcellular pathway.

An overview of current information on the mechanisms by which intestinal calcium absorption occurs is described in this article. Both paracellular and transcellular pathways are analyzed. Special emphasis focuses on molecules participating in the latter pathway, such as TRPV5 and TRPV6 channels, located in the apical region of the enterocytes, CB(9k) and CB(28k), presumably involved in the cation movement from the apical to the basolateral pole of the cell, and PMCA(1b) and Na(+)/Ca(2+) exchanger, proteins that extrude Ca(2+) from the cells. Current concepts on the relative importance of paracellular and transcellular calcium transport and the vitamin D dependence of each pathway are referred and analyzed showing the contrasting views on this issue. More detailed information is given regarding the stimulatory effect of vitamin D on intestinal Ca(2+) absorption either in animal models or in the human intestine. The possible mechanisms triggered by hormones such as PTH, calcitonin, estrogen, thyroid hormone, glucocorticoids and different nutritional factors on intestinal calcium absorption are also reviewed. Finally, the influence of physiological conditions such as growth, pregnancy, lactation and aging on intestinal calcium absorption are discussed.