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Summary Background and objectives The masticatory force affects craniofacial development. We aimed to quantify the topological deviation of the growing craniofacial structure due to soft-food diet feeding and to map the region where the phenotypes appeared on three-dimensional (3D) images. Material and methods Mice were fed a powdered soft diet (SD) or conventional hard diet (HD) of regular rodent pellets at 3 weeks of age until 9 weeks of age. The heads, excluding the mandibles, were scanned by micro-computed tomography. The topographic deviation of the bony surface was quantitatively assessed by a wire mesh fitting analysis. The actual displacement and significant differences were mapped and visualized in each x-, y-, and z-axis on the 3D craniofacial image. On these reconstructed images, two-dimensional linear measurements between the landmark points confirmed the 3D skeletal displacement. Results In the transverse direction, the zygomatic arches and the region in which the temporal muscle attaches to the parietal and temporal bones were narrow in the SD group. The temporal muscle attachment regions significantly shifted anteriorly, and consequently, the sagittal zygomatic arch shortened. Although the cranial sagittal length was not affected, the vertical height was also reduced in the SD group compared to the HD group. Conclusions Our 3D surface-based analysis demonstrated that SD feeding resulted in reduced 3D bony development at the region where the chewing muscles attach to the zygomatic arches and the temporal and parietal bones. Interestingly, SD feeding induced an anterior shift in the temporal and parietal bone regions, which can affect the skeletal inter-jaw relationship.

Rodent incisors grow continuously throughout life, and epithelial progenitor cells are supplied from stem cells in the cervical loop. We report that epithelial Runx genes are involved in the maintenance of epithelial stem cells and their subsequent continuous differentiation and therefore growth of the incisors. Core binding factor β (Cbfb) acts as a binding partner for all Runx proteins, and targeted inactivation of this molecule abrogates the activity of all Runx complexes. Mice deficient in epithelial Cbfb produce short incisors and display marked underdevelopment of the cervical loop and suppressed epithelial Fgf9 expression and mesenchymal Fgf3 and Fgf10 expression in the cervical loop. In culture, FGF9 protein rescues these phenotypes. These findings indicate that epithelial Runx functions to maintain epithelial stem cells and that Fgf9 may be a target gene of Runx signaling. Cbfb mutants also lack enamel formation and display downregulated Shh mRNA expression in cells differentiating into ameloblasts. Furthermore, Fgf9 deficiency results in a proximal shift of the Shh expressing cell population and ectopic FGF9 protein suppresses Shh expression. These findings indicate that Shh as well as Fgf9 expression is maintained by Runx/Cbfb but that Fgf9 antagonizes Shh expression. The present results provide the first genetic evidence that Runx/Cbfb genes function in the maintenance of stem cells in developing incisors by activating Fgf signaling loops between the epithelium and mesenchyme. In addition, Runx genes also orchestrate continuous proliferation and differentiation by maintaining the expression of Fgf9 and Shh mRNA.

Wound healing and tissue regeneration are usually initiated by coagulation followed by fibrous tissue formation. In the present study, we discovered an abundance of connective tissue growth factor (CTGF/CCN2) in human platelets, which was released along with the coagulation process. The CTGF/CCN2 content in platelets was 10-fold higher than that in arterial tissue. Furthermore, the CTGF/CCN2 content in a single platelet was computed to be more than 20-fold higher than that of any other growth factor reported. Considering that CTGF/CCN2 promotes angiogenesis, cartilage regeneration, fibrosis and platelet adhesion, it may be now regarded as one of the major functional components of platelets.