Incorporating supramolecular assemblies of chromophore amphiphiles into covalent hydrogels creates a reusable, robust host for photocatalysis.

Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation can result in Treacher Collins syndrome, Pierre Robin sequence, and cleft palate. Defects in post-migratory neural crest cells can result in pre- or post-ossification defects in the developing craniofacial skeleton and craniosynostosis (premature fusion of cranial bones/cranial sutures). The coronal suture is the most frequently fused suture in craniosynostosis syndromes. It exists as a biological boundary between the neural crest-derived frontal bone and paraxial mesoderm-derived parietal bone. The objective of this review is to frame our current understanding of neural crest cells in craniofacial development, craniofacial anomalies, and the pathogenesis of coronal craniosynostosis. We will also discuss novel approaches for advancing our knowledge and developing prevention and/or treatment strategies for craniofacial tissue regeneration and craniosynostosis.

Bone growth is dependent upon the presence of self-renewing progenitor cell populations. While the contribution of Tissue Nonspecific Alkaline Phosphatase (TNAP) enzyme activity in promoting bone mineralization when expressed in differentiated bone forming cells is well understood, little is known regarding the role of TNAP in bone progenitor cells. We previously found diminished proliferation in the calvarial MC3T3E1 cell line upon suppression of TNAP by shRNA, and in calvarial cells and tissues of TNAP −/− mice. These findings indicate that TNAP promotes cell proliferation. Here we investigate how TNAP mediates this effect. Results show that TNAP is essential for calvarial progenitor cell cycle progression and cytokinesis, and that these effects are mediated by inorganic phosphate and Erk1/2. Levels of active Erk1/2 are significantly diminished in TNAP deficient cranial cells and tissues even in the presence of inorganic phosphate. Moreover, in the absence of TNAP, FGFR2 expression levels are high and FGF2 rescues phospho-Erk1/2 levels and cell cycle abnormalities to a significantly greater extent than inorganic phosphate. Based upon the data we propose a model in which TNAP stimulates Erk1/2 activity via both phosphate dependent and independent mechanisms to promote cell cycle progression and cytokinesis in calvarial bone progenitor cells. Concomitantly, TNAP feeds back to inhibit FGFR2 expression. These results identify a novel mechanism by which TNAP promotes calvarial progenitor cell renewal and indicate that converging pathways exist downstream of FGF signaling and TNAP activity to control craniofacial skeletal development.

A prolonged increase in proinflammatory cytokines is associated with osteoporotic and autoimmune bone loss and, conversely, anti-inflammatory pathways are associated with protection against bone loss. Milk fat globule-epidermal growth factor (MFG-E)-8 is a glycoprotein that is proresolving, regulates apoptotic cell clearance, and has been linked to autoimmune disease and skeletal homeostasis. The role of MFG-E8 in the young vs. adult skeleton was determined in mice deficient in MFG-E8 (KO). In vivo, trabecular bone was similar in MFG-E8KO and wild-type (WT) mice at 6 and 16 wk, whereas 22 wk adult MFG-E8KO mice displayed significantly reduced trabecular BV/TV. The number of osteoclasts per bone surface was increased in 22-wk MFG-E8 KO vs. WT mice, and recombinant murine MFG-E8 decreased the number and size of osteoclasts in vitro. Adult MFG-E8KO spleen weight:body weight was increased compared with WT, and flow cytometric analysis showed significantly increased myeloid-derived suppressor cells (CD11bGR-1) and neutrophils (CD11bLy6G) in MFG-E8KO bone marrow, suggesting an inflammatory phenotype. PTH-treated MFG-E8KO mice showed a greater anabolic response (+124% BV/TV) than observed in PTH-treated WT mice (+64% BV/TV). These data give insight into the role of MFG-E8 in the adult skeleton and suggest that anabolic PTH may be a valuable therapeutic approach for autoimmune-associated skeletal disease.-Michalski, M. N., Seydel, A. L., Siismets, E. M., Zweifler, L. E., Koh, A. J., Sinder, B. P., Aguirre, J. I., Atabai, K., Roca, H., McCauley, L. K. Inflammatory bone loss associated with MFG-E8 deficiency is rescued by teriparatide.