The bone morphogenetic protein (BMP) signaling pathway is highly conserved across many species, and its importance for the patterning of the skeletal system has been demonstrated. A disrupted BMP signaling pathway results in severe skeletal defects. Murine calvaria has been identified to have dual-tissue lineages, namely, the cranial neural-crest cells and the paraxial mesoderm. Modulations of the BMP signaling pathway have been demonstrated to be significant in determining calvarial osteogenic potentials and ossification in vitro and in vivo. More importantly, the BMP signaling pathway plays a role in the maintenance of the homeostasis of the calvarial stem cells, indicating a potential clinic significance in calvarial bone and in expediting regeneration. Following the inherent evidence of BMP signaling in craniofacial biology, we summarize recent discoveries relating to BMP signaling in the development of calvarial structures, functions of the suture stem cells and their niche and regeneration. This review will not only provide a better understanding of BMP signaling in cranial biology, but also exhibit the molecular targets of BMP signaling that possess clinical potential for tissue regeneration.

Background The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest‐derived frontal bone vs. mesoderm‐derived parietal bone). Neural crest‐derived frontal bone exhibits superior osteogenic activities and bone regeneration. MicroRNA (miRNA) has been emerged as a crucial regulator during organogenesis and is involved in a range of developmental processes. However, the underlying roles of miRNA regulation in frontal bone and parietal bone is unknown. Results Total of 83 significantly expressed known miRNAs were identified in frontal bones versus parietal bones. The significantly enriched gene ontology and KEGG pathway that were predicted by the enrichment miRNAs were involved in several biological processes (cell differentiation, cell adhesion, and transcription), and multiple osteogenic pathways (e.g., focal adhesion, MAPK, VEGF, Wnt, and insulin signaling pathway. Focal adhesion and insulin signaling pathway were selected for target verification and functional analysis, and several genes were predicted to be targets genes by the differentially expressed miRNAs, and these targets genes were tested with significant expressions. Conclusions Our results revealed a novel pattern of miRNAs in murine calvaria with dual tissue origins, and explorations of these miRNAs will be valuable for the translational studies to enhance osteogenic potential and bone regeneration in the clinic.

Heart disease remains the leading cause of morbidity and mortality worldwide. Induced pluripotent stem cells (iPSCs) have the ability to differentiate into cardiomyocytes (CMs), rendering this cell type to be a promising precursor of cardiomyocytes for cell-based cardiac regeneration. Obtaining CMs with a high yield and purity coupled with improved subsequent survival could prove to be invaluable for the future cell replacement therapeutic strategies. Rho-associated protein kinase (ROCK) is involved in a wide range of fundamental cellular functions and serves significant roles in cardiac physiology. In the present study, human (h)iPSC-CMs were generated from iPSCs by including glycogen synthase kinase 3β and Wnt inhibitors in the basal culture media. The possible effect of Y27632, a ROCK inhibitor, on hiPSC-CMs was then investigated. hiPSC-CMs of high purity were harvested with >96% of cells expressing cardiac troponin T. Additionally, treatment with 10 µM Y27632 significantly improved the viability of dissociated hiPSC-CMs. The effects of ROCK inhibitors Y27632 and fasudil, on the proliferation and apoptosis of hiPSC-CMs were also examined. Treatment with ROCK inhibitors markedly enhanced hiPSC-CM proliferation, by up to 2.5-fold, whilst Y27632 treatment reduced apoptosis in hiPSC-derived CMs under serum starvation and suspension by suppressing the expression of caspase-3. Taken together, data from the present study indicated that ROCK kinase inhibitors effectively improved the cultural system of hiPSC-derived CMs.