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Calvarial bones are connected by fibrous sutures. These sutures provide a niche environment that includes mesenchymal stem cells (MSCs), osteoblasts, and osteoclasts, which help maintain calvarial bone homeostasis and repair. Abnormal function of osteogenic cells or diminished MSCs within the cranial suture can lead to skull defects, such as craniosynostosis. Despite the important function of each of these cell types within the cranial suture, we have limited knowledge about the role that crosstalk between them may play in regulating calvarial bone homeostasis and injury repair. Here we show that suture MSCs give rise to osteoprogenitors that show active bone morphogenetic protein (BMP) signalling and depend on BMP-mediated Indian hedgehog (IHH) signalling to balance osteogenesis and osteoclastogenesis activity. IHH signalling and receptor activator of nuclear factor kappa-Β ligand (RANKL) may function synergistically to promote the differentiation and resorption activity of osteoclasts. Loss of Bmpr1a in MSCs leads to downregulation of hedgehog (Hh) signalling and diminished cranial sutures. Significantly, activation of Hh signalling partially restores suture morphology in Bmpr1a mutant mice, suggesting the functional importance of BMP-mediated Hh signalling in regulating suture tissue homeostasis. Furthermore, there is an increased number of CD200+ cells in Bmpr1a mutant mice, which may also contribute to the inhibited osteoclast activity in the sutures of mutant mice. Finally, suture MSCs require BMP-mediated Hh signalling during the repair of calvarial bone defects after injury. Collectively, our studies reveal the molecular and cellular mechanisms governing cell–cell interactions within the cranial suture that regulate calvarial bone homeostasis and repair.

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Craniofacial development depends on cell-cell interactions, coordinated cellular movement and differentiation under the control of regulatory gene networks, which include the distal-less (Dlx) gene family. However, the functional significance of in patterning the oropharyngeal region has remained unknown. Here, we show that loss of leads to a shortened soft palate and an absence of the levator veli palatini, palatopharyngeus and palatoglossus muscles that are derived from the 4th pharyngeal arch (PA); however, the tensor veli palatini, derived from the 1st PA, is unaffected. Dlx5-positive cranial neural crest (CNC) cells are in direct contact with myoblasts derived from the pharyngeal mesoderm, and disruption leads to altered proliferation and apoptosis of CNC and muscle progenitor cells. Moreover, the FGF10 pathway is downregulated in mice, and activation of FGF10 signaling rescues CNC cell proliferation and myogenic differentiation in these mutant mice. Collectively, our results indicate that plays crucial roles in the patterning of the oropharyngeal region and development of muscles derived from the 4th PA mesoderm in the soft palate, likely via interactions between CNC-derived and myogenic progenitor cells.

Magnesium–zinc–calcium (Mg–Zn–Ca) alloys have attracted increasing attention for biomedical implant applications, especially for bone repair, because of their biocompatibility, biodegradability, and similar mechanical properties to human bone. The objectives of this study were to characterize Mg–2 wt % Zn–0.5 wt % Ca (named ZC21) alloy pins microstructurally and mechanically, and determine their degradation and interactions with host cells and pathogenic bacteria in vitro and in vivo in comparison with the previously studied Mg–4 wt % Zn–1 wt % strontium (named ZSr41) alloy and Mg control. Specifically, the in vitro degradation and cytocompatibility of ZC21 pins with bone marrow derived mesenchymal stem cells (BMSCs) were investigated using both direct culture and direct exposure culture methods. The adhesion density of BMSCs on ZC21 pins (i.e., direct contact) was significantly higher than on pure Mg pins in both in vitro culture methods; the cell adhesion density around ZC21 pins (i.e., indirect contact) was similar to the cell-only positive control in both in vitro culture methods. Interestingly, ZC21 showed a higher daily degradation rate, crack width and crack area ratio in the direct exposure culture than in the direct culture, suggesting different culture methods did affect its in vitro degradation behaviors. When cultured with Gram-positive bacteria methicillin-resistant Staphylococcus aureus (MRSA), ZC21 reduced bacterial adhesion on the surface more significantly than that of ZSr41 and Mg. The in vivo degradation and biocompatibility of the ZC21 pins for bone regeneration were studied in a mouse femoral defect model. The in vivo degradation rate of ZC21 pins was much slower than that of ZSr41 alloy and Mg control pins. After 12 weeks of implantation in vivo, the ZC21 group showed the shortest gap at the femoral defect, indicating that ZC21 pins promoted osteogenesis and bone healing more than ZSr41 and Mg control pins. Overall, the ZC21 alloy is promising for bone repair, while providing antibacterial activities, and should be further studied toward clinical translation.

No abstract

The results do not prove sufficient to justify elective treatment of the neck in primary cN0 lip SCC and close observation would be a viable option in such cases. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1392-1400, 2015.

Background As the rate-limit enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) plays important roles in tumour progression, but the exact mechanism through which G6PD controls cancer metastasis remains unclear. Methods G6PD expression in resected oral squamous cell carcinoma (OSCC) samples was analysed by immunohistochemistry. The effects and mechanism of G6PD suppression on OSCC cell lines were measured by transwell assay, wound healing assay, western and lectin blot, mass spectrometer analysis, ChIP-PCR, and luciferase reporter assay. BALB/c-nude mice were used to establish orthotopic xenograft model. Results G6PD expression in the tumours of 105 OSCC patients was associated with lymphatic metastasis and prognosis. In vitro cellular study suggested that G6PD suppression impaired cell migration, invasion, and epithelial-mesenchymal transition. Furtherly, G6PD knockdown activated the JNK pathway, which then blocked the AKT/GSK-3β/Snail axis to induce E-Cadherin expression and transcriptionally regulated MGAT3 expression to promote bisecting GlcNAc-branched N-glycosylation of E-Cadherin. An orthotopic xenograft model further confirmed that dehydroepiandrosterone reduced lymphatic metastatic rate of OSCC, which was partially reversed by JNK inhibition. Conclusions Suppression of G6PD promoted the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin via activating the JNK pathway, which thus acted on OSCC metastasis.