Targeting miRNAs in Osteoblast Differentiation under Malnutrition Conditions

Aims: Previous studies reported that reduced bone formation was identified in fasting adult female mice compared with the ad libitum control group. An increasing number of studies have shown that miRNAs contribute to bone homeostasis. Unfortunately, there are minor concerns about the underlying mechanisms in osteoblastic differentiation under malnutrition conditions. Methods: We investigated microRNAs (miRNAs) in osteoblastic differentiation under malnutrition conditions using high-throughput bioinformatics approaches. To screen for targeted microRNAs, sequences were quantified by aligning reads to miRbase using miRDeep2 software. Unadjusted p-values were calculated using the Student’s t-test. Genes with a p-value of <0.05 and log 2FC (fold change) ≥ 1 were considered differentially expressed genes (DEGs). DEGs were submitted to Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, respectively. Results: They were mainly enriched in biological process terms type and biological pathways, respectively. Particularly, we evaluated seven microRNAs, mir-494 3p, mir-466, mir-455, mir-708, mir-298, mir-92 and mir-224, which likely play roles in osteoblastogenesis in fasting adult mice. Conclusion: To our knowledge, this is the first study on the expression pattern of miRNA in osteoblasts of malnourished adult mice. These targeting miRNAs may provide a potential therapeutic approach to treat osteoporosis.

Essential role of Msx1 in regulating anterior-posterior patterning of the secondary palate in mice

Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(Rosa Msx1^(Wnt1-Cre))throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in Rosa Msx1^(Wnt1-Cre)mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medialposterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells,suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.

Regio-and stereo-selective olefinic C–H functionalization of aryl alkenes in ethanol

We report on N,N-bidentate-chelation-assistedα-and β-olefinic C–H alkenylation of aryl alkenes in ethanol to afford aryl dienes/trienes with excellent regio-and stereo-selectivities.The reaction of 2-alkenyl benzylamine and benzoic acid derived substrates proceeded through six-membered exo-cyclo-metallation and seven-membered endo-cyclometallation.The aerobic protocols feature wide functional-ity tolerance,high selectivities and yields,mild conditions and scalable preparation,and the directing group can be easily removed to afford Boc-protected amine by simple reduction.