USC University of Southern California

Study Indicates Dentin May Not Be Needed for Enamel Formation

A study led by Yang Chai of the Ostrow School of Dentistry of USC and published in the April 2011 issue of Development had some surprising results that appear to challenge long-held ideas about normal tooth development.

“SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis” examined the effects of certain cell signaling problems on the formation of structures in the mouth and face. Two cell signaling pathways called TGF-beta and BMP are known to control the destiny of cranial neural crest (CNC) cells during jaw and tooth formation, and one protein, SMAD4, can mediate the activity of both pathways.

In this study, Chai and his team investigated what happened when the gene for the SMAD4 protein was inactivated in mice. With no SMAD4 to regulate the pathways, problems arose with the proper formation of odontoblasts – the cells that grow bone tissue – and also with the formation of dentin, an important protein for teeth.

Because of the missing SMAD4 protein, small bony structures had replaced the dentin within the malformed teeth. But surprisingly, the hard outer coating of enamel was completely healthy and normal.

Chai stated that the malformations in the teeth were a result of SMAD4’s connection to another signaling pathway called WNT. SMAD4’s absence allowed WNT to shift into overdrive and redirected neural crest cells to form bone, instead of dentin.

“This discovery has very important clinical implications,” Chai said. “For example, we can generate artificial enamel for restorative purposes in the future that does not require dentin matrix as a substrate. Instead, we can use readily available bone matrix to support enamel formation.”

It is much easier to get bone than dentin for the purpose of enamel regeneration, Chai said. And there also appears to have been precedent for this kind of surprising enamel growth.

“It turns out that the prehistoric fish had similar structures in which enamel formed on bony scales,” he said.