Abstract
gp130-mediated signaling is involved in both chondrogenesis and osteogenesis, but its direct role in the formation of embryonic Meckel's cartilage and associated mandibular development has not yet been elucidated. In this study, we examined the influence of gp130 ablation on the developing mandibular Meckel's cartilage by evaluating the morphological and histological changes as well as the gene expression patterns in developing embryonic gp130-/- mice. The ablation of the gp130 gene showed no change in region-specific collagen mRNA expression except for a slight delay in its expression but caused shortened embryonic Meckel's cartilage, delayed hypertrophic chondrocyte maturation and subsequent bony replacement with characteristic bending of the intramandibular Meckel's cartilage. The bending of Meckel's cartilage led to a narrow mandibular arch at the rostral area with poor cortical plate formation. These findings indicate that gp130-mediated signaling is important for the normal morphogenesis of Meckel's cartilage and subsequent mandibular development.
Highlights
The various histological morphogenetic events that occur during embryonic mandibular development depend on the proper formation of Meckel’s cartilage, which serves as the primordium of the mandible and guides its early morphogenesis
A variety of growth factors, such as EGF (Shum et al, 1993), fibroblast growth factor (FGF) (Wilson and Tucker, 2004), TGF (Ito et al, 2002) and hepatocyte growth factor (HGF) (Amano et al, 1999), and a complicated bone morphogenetic protein (BMP)-Msx-FGF signaling network participate in the initiation and maintenance of chondrogenesis of Meckel’s cartilage and osteogenesis of the mandible (Macdonald and Hall, 2001; Wilson and Tucker, 2004)
Parathyroid hormone related protein (PTHrP), which shares a receptor with parathyroid hormone (PTH), constitutes a signaling pathway that negatively regulates the rate of chondrocyte differentiation in endochondral bone formation during embryogenesis (Yamazaki et al, 1997; Long and Linsenmayer, 1998)
Summary
The various histological morphogenetic events that occur during embryonic mandibular development depend on the proper formation of Meckel’s cartilage, which serves as the primordium of the mandible and guides its early morphogenesis. Gp130-associated cytokines such as IL-6, IL-11, leukemia inhibit factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1) share the ubiquitously expressed common signal transducing receptor component gp130 and make up a cytokine family based on their common structure and function. These cytokines bind with their cognate receptors and form a receptor complex by inducing homodimerization or heterodimerization of gp130 with LIF receptor or OSM receptor for signal transduction. The gp130-mediated signaling triggered by gp130-associated cytokines induces diverse biologic functions in immune, hematopoietic, and nervous systems as well as in bone (Taga and Kishimoto, 1997; Betz et al, 1998; Bravo and Heath, 2000)
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