Epigenetic effects on cell signalling leads healthy stem cells to create benign fibromas in the jaw
Thursday, 07 November 2013
This is Professor Songtao Shi of the Ostrow
School of Dentistry at the University of Southern
California. Credit: John Skalicky.
Principal investigator Songtao Shi, professor at the Ostrow School of Dentistry Center for Craniofacial Molecular Biology, says ossifying fibromas, the tumours focused on in the study, are benign but can grow aggressively and cause progressive enlargement of the jaw.
"The only treatment option for ossifying fibromas is surgical, which leads to major loss of vital tissues and challenging post-surgical reconstruction," Shi says.
"Quality of life is largely compromised. Thus, there is an urgent need to understand the underlying mechanism by which stem cells may contribute to the pathophysiology of oro-facial benign tumours and to develop target-specific treatment."
Shi and his collaborators uncovered a cellular signalling pathway that converts healthy mesenchymal stem cells in the jaw into ossifying fibroma mesenchymal stem cells (OFMSC), lessening their ability to make healthy bone tissue and greatly increasing the rate at which they multiply. The tumour stem cells display increased signalling activity with TGF-beta (TGF-b), a signalling protein already shown to be heavily tied to other craniofacial malformations.
Epigenetic up-regulation – switching existing but inactive genes "on" – of the TGF-b cell signalling loop appears to increase the formation of ossifying fibroma tumours. Conversely, suppressing TGF-b signalling seems to quell the tumour's proliferation rate, Shi says.
While there is still much more investigation needed, Shi says hopes that the findings have shed light on a way to stop the harmful growth of the tumours before risky surgery is needed.
"With an increased understanding of the mechanism of OFMSC, we can induce them to turn into normal jawbone MSC," he says.
"But before we can put this into clinical use, more translational research is needed."
Contact: Beth Newcomb
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