MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in regulating many biological processes, including myogenic differentiation and muscle development. miR-29 is a promoting factor during myogenesis but its full spectrum of impact on muscle cells has yet to be explored. Here we describe an analysis of miR-29 affected transcriptome in C2C12 muscle cells using a high throughput RNA-sequencing platform. The results reveal that miR-29 not only functions to promote myogenic differentiation but also suppresses the transdifferentiation of myoblasts into myofibroblasts. miR-29 inhibits the fibrogenic differentiation through down-regulating both extracellular matrix genes and cell adhesion genes. We further demonstrate that miR-29 is under negative regulation by TGF-beta (TGF-β)–Smad3 signaling via dual mechanisms of both inhibiting MyoD binding and enhancing Yin Yang 1 (YY1)-recruited Polycomb association. Together, these results identify miR-29 as a pleiotropic molecule in both myogenic and fibrogenic differentiation of muscle cells.

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Objectives: Bone regeneration by bone tissue engineering is a therapeutic option for bone defects. Improving the osteogenic differentiation of mesenchymal stem cells (MSCs) is essential for successful bone regeneration. We previously showed that AP2a enhances the osteogenic differentiation in MSCs. The present study investigated the mechanism of how AP2a regulates the direct differentiation. Materials and methods:Co-immunoprecipitation and ChIP assays were carried out to investigate the underlying mechanism in MSCs differentiation. The osteogenic differentiation potential was determined by mineralization ability and the expression of osteogenic marker in vitro and the in vivo bone-like tissue generation in nude mice. Results:We show that AP2a can compete with RUNX2, a key transcription factor in osteogenic differentiation, to recruit YAP and release the inhibition of RUNX2 activity from YAP by forming YAP-AP2a protein complex. YAP-AP2a protein complex also interacts with the BARX1 promoter through AP2a, inhibit the transcription of BARX1. Moreover, BARX1 inhibits osteogenic differentiation of MSCs.Conclusions: Our discoveries revealed that AP2a may regulate the osteogenic differentiation in an indirect way through competing with RUNX2 to relieve the RUNX2 activity which inhibited by YAP, and also in a direct way via targeting the BARX1 and directly repressed its transcription. Thus, our discoveries shed new light on the mechanism of direct differentiation of MSCs and provide candidate targets for improving the osteogenic differentiation and enhancing bone tissue regeneration.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

2,5-Furandicarboxylic acid (FDCA), which is currently prepared by catalyzing the oxidation of 5-hydroxymethylfurfural (HMF), is a biobased platform compound with broad market prospects. Herein, a detailed free-radical chain reaction mechanism consisting of both main and side reaction pathways was proposed to describe the liquid-phase air oxidation process of 5hydroxymethylfurfural to 2,5-furandicarboxylic acid over a Co/ Mn/Br catalyst. The higher reactivity of the hydroxymethyl group than the aldehyde group for HMF oxidation was first explained according to the retardation effect of alcohols on free-radical reactions and the reactive activity of active hydrogen on the two substituents of HMF. Considering the low stability of HMF, the possible side reactions including condensation, decarboxylation, decarbonylation, and ring-opening for HMF oxidation were further investigated. Subsequently, to obtain more reliable model parameters, a lumped kinetic scheme was developed considering only the formation of important and detectable reactants, intermediates, and products. Since the total reaction rate is not sensitive to the reactant concentration, a fractional kinetic model was adopted to correlate the experimental results and evaluate the kinetic parameters.