Abstract 26

The role of urothelium in the ectopic formation of bone in skeletal muscle.

Dr. Christopher Podagiel, Dr. Ben Goss, Dr. Yin Xiao, Prof. Ross Crawford, A/Prof. Richard Williams.

Queensland University of Technology.

This research aims to study the bone forming reaction that occurs when the lining of the urinary bladder is transplanted into skeletal muscle. By obtaining a greater understanding of this reaction, it may be possible to define and isolate further factors that may be applied as osteoinductive agents in orthopaedic surgery (such as bone morphogenetic proteins).

Using species that have demonstrated strong osteogenic potential, three different series will see three types of tissue from guinea pigs (urothelium, cultured urothelial cells, and cultured urothelial cells labelled with green fluorescent protein), transplanted into congenitally immunodeficient mice (SCID-mice). Mice will then be sacrificed after six weeks for implant site tissue studies.

It is anticipated that transplanted urothelial tissue will induce ectopic ossification in skeletal muscle. It is also anticipated that cultured urothelial cells will induce ectopic ossification, demonstrating that only urothelial cells (and not underlying stroma) need to be present to cause the reaction.

Further, when any new bone formed after the implantation of GFP-labelled urothelial cells is studied, it is hoped that osteoblasts within the newly formed bone will also express GFP. This would strongly suggest the osteoblasts are derived from the urothelial cells themselves, and not from muscle-bound cells (such as mesenchymal stem cells) that have been influenced by the juxtaposition of urothelial cells. This would strongly imply that urothelial cells had "de-differentiated" from their epithelial phenotype by way of an epithelial-mesenchymal transition to a stem-cell phenotype, and then re-differentiated along osteogenic lines.

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