Laminin, VEGF, and bone matrix protein expression in uroepithelial bone induction--a canine model

A biological and embryological bone induction from epithelial-mesenchymal cell interactions has been noticed in some developing tissues. However, the mechanism for bone formation induced by the epithelial-mesenchymal cell interactions is not clear. The aim of our study was to reveal the role of laminin, vascular endothelial growth factor (VEGF), and bone matrix proteins in mesenchymal cell differentiation during uroepithelial bone induction using a well-established canine model. In this model, a myoperitoneal muscle flap from the abdominal rectus sheath was transplanted into the bladder wall. After 6 weeks, the bladder samples were removed and assessed by histology and immunohistochemistry. This study demonstrated that bone formation occurred in two different directions with two distinct mechanisms. We noted that bone-forming cells in two types of bone formation derived from mesenchymal stem cell differentiation induced either from uroepithelium or bone autoinduction. Laminin was only expressed in peripheral regions of uroepithelium bone formation. Type II collagen was expressed both intracellularly and extracellularly around hypertrophic chondrocytes, whereas VEGF was mostly expressed in proliferating chondrocytes. This study indicates that components in basement membrane like laminin play a role in transitional epithelium-induced differentiation of mesenchymal cells to chondrocytes in muscle tissue. The sequential expression of bone matrix proteins by differentiated osteogenetic cells indicates a subsequent sequence of bone autoinduction.