Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D3 (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (>1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts.
The mRNA-destabilizing protein ZFP36 has been previously described as a tumor suppressor whose expression is lost during colorectal cancer development. In order to evaluate its role in this disease, we restored ZFP36 expression in different cell contexts, showing that the presence of this protein impairs the epithelial-to-mesenchymal transition (EMT) and induces a higher susceptibility to anoikis. Consistently, we found that ZFP36 inhibits the expression of three key transcription factors involved in EMT: ZEB1, MACC1 and SOX9. Finally, we observed for the first time that its expression negatively correlates with the activity of Wnt/β-catenin pathway, which is constitutively activated in colorectal cancer. This evidence provides a clue on the mechanism leading to the loss of ZFP36 in CRC.
Summary
Background Several reports indicate that mesalazine (5‐aminosalicylic acid, 5‐ASA) is a promising candidate for the chemoprevention of colo‐rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti‐inflammatory drugs. This activity of 5‐ASA is probably the consequence of a number of effects determined on colo‐rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of β‐catenin signalling could induce these cellular effects.
Aim To characterize better the capacity of 5‐ASA to inhibit the β‐catenin signalling pathway.
Methods Genes belonging to the β‐catenin signalling pathway were analysed in colo‐rectal cancer cell lines treated with 5‐ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity.
Results The results obtained indicated that 5‐ASA induces the expression of a protein called μ‐protocadherin that belongs to the cadherin superfamily and is able to sequester β‐catenin on the plasmatic membrane of treated cells hampering its function.
Conclusion These findings suggest that μ‐protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5‐ASA.
ZFP36L1 negatively regulates erythroid differentiation of human hematopoietic progenitors by directly binding the 3′ UTR of Stat5b mRNA, thereby triggering its degradation. This study shows that posttranscriptional regulation is involved in the control of hematopoietic differentiation.
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