Abstract
Calvarial bones arise from two embryonic tissues, namely, the neural crest and the mesoderm. In this study we have addressed the important question of whether disparate embryonic tissue origins impart variable osteogenic potential and regenerative capacity to calvarial bones, as well as what the underlying molecular mechanism(s). Thus, by performing in vitro and in vivo studies, we have investigated whether differences exist between neural crest–derived frontal and paraxial mesodermal–derived parietal bone. Of interest, our data indicate that calvarial bone osteoblasts of neural crest origin have superior potential for osteogenic differentiation. Furthermore, neural crest–derived frontal bone displays a superior capacity to undergo osseous healing compared with calvarial bone of paraxial mesoderm origin. Our study identified both in vitro and in vivo enhanced endogenous canonical Wnt signaling in frontal bone compared with parietal bone. In addition, we demonstrate that constitutive activation of canonical Wnt signaling in paraxial mesodermal–derived parietal osteoblasts mimics the osteogenic potential of frontal osteoblasts, whereas knockdown of canonical Wnt signaling dramatically impairs the greater osteogenic potential of neural crest–derived frontal osteoblasts. Moreover, fibroblast growth factor 2 (FGF-2) treatment induces phosphorylation of GSK-3β and increases the nuclear levels of β-catenin in osteoblasts, suggesting that enhanced activation of Wnt signaling might be mediated by FGF. Taken together, our data provide compelling evidence that indeed embryonic tissue origin makes a difference and that active canonical Wnt signaling plays a major role in contributing to the superior intrinsic osteogenic potential and tissue regeneration observed in neural crest–derived frontal bone. © 2010 American Society for Bone and Mineral Research.
Highlights
The vertebrate dermal skull roof is an ancient structure formed from membranous bones that are evolutionarily derived from the protective dermal plates of early jawless fishes.[1]
The distinct contributions of each tissue to the skull have been well established by combining mice with a Wnt1-Cre construct and a conditional reporter gene, R26R.(2,3) These studies have defined the pattern of cranial neural crest cell migration in mouse embryos and demonstrated that the frontal bone is of neural crest origin, whereas the parietal bone is of mesoderm origin
Knowledge regarding of the embryonic origins of mammalian frontal and parietal bones has prompted us to ask the question, ‘‘Do differences in embryonic tissue origin translate into differences in biologic activity on a cellular and molecular level?’’ To address this question, we have investigated, in vitro and in vivo, the osteogenic differentiation potential and calvarial healing capacity of both frontal and parietal bones
Summary
The vertebrate dermal skull roof is an ancient structure formed from membranous bones that are evolutionarily derived from the protective dermal plates of early jawless fishes.[1]. The distinct contributions of each tissue to the skull have been well established by combining mice with a Wnt1-Cre construct and a conditional reporter gene, R26R.(2,3) These studies have defined the pattern of cranial neural crest cell migration in mouse embryos and demonstrated that the frontal bone is of neural crest origin, whereas the parietal bone is of mesoderm origin. The Wnt signaling pathway is an important regulator of cellular differentiation in a variety of cell types, including osteoblasts.[12,13,14,15,16] It plays a widespread role in skeletogenesis, spanning from embryonic skeletal patterning through fetal skeletal development and bone remodeling.[17,18] Wnt proteins act on target cells by binding to Frizzleds (Fzs), seven-span transmembrane receptor proteins, and LRP-5/6, single-span transmembrane coreceptor proteins. Activation of Dvl leads to the inhibition of glycogen synthase kinase 3b (GSK-3b [22,23,24]), preventing b-catenin degradation by the protein complexes consisting of GSK-3b, axin, and adenomatous polyposis coli (APC).(23) since b-catenin cannot be targeted for degradation, cytoplasm accumulation transpires, followed by subsequent translocation to the nucleus, where in concert with members of the T cell factor/lymphoid enhancer factor (TCF/LEF) family, it activates transcription of a wide range of genes, including c-myc, cyclin D1, and axin-2.(25–27)
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