Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSC differentiation. Here, we investigated FBXL11, a histone demethylase, lysine (K)-specific demethylase 2A, which is evolutionarily conserved, ubiquitously expressed, and a member of the JmjC-domain-containing histone demethylase family. We tested whether FBXL11 could inhibit the osteo/dentinogenic differentiation potential in MSC cells with gain-and loss-of-function assays. We found that FBXL11 regulated osteo/dentinogenic differentiation in MSC cells. Furthermore, we found that the gene encoding the epidermal growth factor, Epiregulin (EREG), was a downstream target of FBXL11, and that EREG mediated FBXL11 regulation of MSC differentiation. Moreover, we found that the FBXL11 histone demethylase function was activated by associating with BCL6 corepressor, and this complex could repress EREG transcription by increasing histone K4/36 methylation in the EREG promoter. In conclusion, our results elucidated a new function for FBXL11 and EREG, explored the molecular mechanism underlying directed differentiation in MSC cells, and identified potential target genes for improving tissue regeneration techniques. STEM CELLS 2013;31:126-136 Disclosure of potential conflicts of interest is found at the end of this article.

Here we report the novel function of heat shock protein 90 in regulating autophagy and apoptosis in human acute promyelocytic leukemia (APL)-derived NB4 cells, via decreased nuclear factor-κB activity and nucleus translocation, thus leading to down-regulation of autophagy-related component Beclin1. This study may be helpful in understanding the detail mechanism for sodium selenite in APL therapy.

Recent studies have shown that secretion of bioactive factors from mesenchymal stem cells (MSCs) plays a primary role in MSC-mediated therapy; especially for bone marrow-derived MSCs (BMSCs). MSCs from dental apical papilla (SCAPs) are involved in root development and may play a critical role in the formation of dentin and pulp. Bioactive factors secreted from SCAPs actively contribute to their environment; however, the SCAPs secretome remains unclear. To address this and gain a deeper understanding of the relevance of SCAPs secretions in a clinical setting, we used isobaric chemical tags and high-performance liquid chromatography with tandem mass spectrometry to profile the secretome of human SCAPs and then compared it to that of BMSCs. A total of 2,046 proteins were detected from the conditioned medium of SCAPs, with a false discovery rate of less than 1.0%. Included were chemokines along with angiogenic, immunomodulatory, antiapoptotic, and neuroprotective factors and extracellular matrix (ECM) proteins. The secreted levels of 151 proteins were found to differ by at least twofold when BMSCs and SCAPs were compared. Relative to BMSCs, SCAPs exhibited increased secretion of proteins that are involved in metabolic processes and transcription and lower levels of those associated with biological adhesion, developmental processes, and immune function. In addition, SCAPs secreted significantly larger amounts of chemokines and neurotrophins than BMSCs, whereas BMSCs secreted more ECM proteins and proangiogenic factors. These results may provide important clues regarding the molecular mechanisms associated with tissue regeneration and how they differ between cell sources.

PDLSC-mediated periodontal tissue regeneration is considered a promising method for periodontitis treatment, but the supply of PDLSCs is limited. As a potential alternative, WJCMSCs are readily available; however, there is a lack of evidence proving that WJCMSCs are suitable for periodontal tissue regeneration. In this study, we investigated the characteristics of WJCMSCs and PDLSCs. We found the osteo-/dentinogenic, adipogenic and chondrogenic differentiation potentials of PDLSCs were more powerful than those of WJCMSCs. Microarray analysis discovered that 903 genes were significantly down-regulated and 726 genes up-regulated in WJCMSCs compared with PDLSCs. Based on the microarray data, we found that several genes may be associated with MSCs characteristics. Further bioinformatic analysis identified that TGF-β and WNT signaling pathways, and several genes, including STAT5B and ITGA4, may play key roles in MSCs. Our results indicate that the differentiation potentials of WJCMSCs are far less than those of PDLSCs, and that unmodified WJCMSCs may not be good seeding cells for periodontal tissue regeneration. Our results also help to elucidate the differentiation mechanisms in MSCs and to find the key factors to prompt WJCMSC-mediated periodontal tissue regeneration.