Endogenous bone morphogenetic protein expression in transplants of urinary bladder.

Abstract

Bone morphogenetic proteins (BMP) were identified in full-thickness autogeneic implants of the urinary bladder by monoclonal antibody BMP immunohistochemistry and by in situ hybridization of BMP-2, -4, and -5 mRNAs. Within the first week after transplantation, BMP mRNAs were expressed in uroepithelial cytoplasm and basement membranes of proliferating cells. About the second week, BMP-2, -4, and -5 mRNA expression and monoclonal antibody BMP-2 synthesis were colocalized in the sites of conversion of transitional to columnar epithelium. In close association with basement membrane, mesenchymal-type cells migrated, proliferated, and formed osteogenetic condensations. The areas of condensation were composed of densely packed cells with high nucleocytoplasmic ratios and high mitotic activity, and resembled periosteum of growing membrane bone. For the first 3 to 4 weeks, the bone deposits grew rapidly in size on surfaces of columnar uroepithelial basement membrane. After 4 to 5 weeks, the growth was constrained by enclosure in a thick, dense, periosteum-like fibrous tissue, completely separated from basement membrane. Serial observations are submitted herewith as circumstantial evidence that bone development is a product of mutual interaction of uroepithelium and mesenchymal-type cells across basement membranes in response to endogenous BMP-2, -4, and -5. Neither BMP-2, -4, -5 mRNA nor monoclonal antibody BMP-2 was detected in the lamina propria, smooth muscle, or fibrous tissue.