Researchers at the Herman Orstrow School of Dentistry at the University of Southern California have discovered how epigenetic regulation can control root patterning and development, which may lead to techniques and technologies for regrowing the roots of teeth.
Epigenetics is the study of changes in organisms caused by the modification of gene expression, rather than the alteration of the genetic code itself.
“This is an aspect that doesn’t involve change in the DNA sequence, but it’s basically through the control where you make the genes available or unavailable for transcription, which can determine the pattern,” said Yang Chai, DMD, PhD, DDS, associate dean for research at the school.
A protein called Ezh2 helps the bones of the face to develop, but how it affects tooth root development was not understood, the researchers said. So, they examined what happens when Ezh2 isn’t present in the molars of developing mice.
The researchers found that Ezh2 and another protein called Arid1a must be in balance to establish the tooth root pattern and the proper integration of roots with the jawbones. Chai called the new work motivating.
“I feel excited about this because, through human evolution, there have been changes in our diet and environment that can influence our epigenome—the ways our genes are regulated—and you can clearly see a difference between the root formation of our dentition versus Neanderthals,” Chai said.
Neanderthal molars have longer root trunks than the ones seen in anatomically modern humans and show late splitting of the roots, which could be due to the effect of diet and exercise on the proteins that turn the genes on and off.
The balance of regulators also plays a role in disease and wellness. In different types of cancer, research has shown that the balance of two opposing epigenetic regulators is quite important. Knocking out the one regulator can create cancer, Chai said, but modulating its opposing regulator can stop the cancer.
“These epigenetic regulators, which are not changing the DNA sequences, are important in themselves, but their level of activity is also important,” Chai said. “Basically, you can’t have too much or too little. If the balance is off track, then you get developmental problems or disease.”
While the researchers say their ultimate goal is to regrow teeth, generating an entire tooth is challenging because it takes a long time for nature to build a tooth up from development to eruption, Chai said. So, the researchers are looking to find ways to regenerate a molar root and put a crown on top.
“It would be the best of both worlds: a natural integration of the root with the jawbone with the periodontal ligament in place, and a reduction in the amount of time we need by using just a crown to restore function,” Chai said.
The study, “Antagonistic Interaction Between Ezh2 and Arid1a Coordinates Root Patterning and Development Via Cdkn2a in Mouse Molars,” was published by eLife.