Why some oral inflammatory diseases progress much more rapidly than others

 A team of researchers from VCU Massey Comprehensive Cancer Center, the VCU School of Dentistry and the University of Pennsylvania recently published a study in Nature Communications examining why some oral inflammatory diseases progress much more rapidly than others.

The study was co-led by Kang I. Ko, D.D.S., Ph.D., of the University of Pennsylvania, Jinze Liu, Ph.D., of VCU, and Kevin Matthew Byrd, D.D.S., Ph.D., of VCU, with co-first authors Quinn T. Easter, Ph.D., and Khoa L.A. Huynh, Ph.D. The findings identified previously unrecognized changes in blood vessels that may help researchers better understand tissue destruction in oral disease and provide insights relevant to other inflammatory conditions, including cancer.

To conduct this study, the research team used and expanded a tool they created, the Human Periodontal Atlas—the leading periodontal atlas in the world—as part of the wider Human Cell Atlas, a single cell atlas built from existing publicly available data sets, to examine RNA patterns across different cell types.

“It’s a lot like building really complicated LEGO structures,” said Byrd, a member of the Cancer Biology research program at Massey and assistant professor of oral and craniofacial molecular biology at the VCU School of Dentistry. “Each dataset gives us another set of pieces. By putting them together, we can see which disease patterns are unique to one condition and which ones show up across related inflammatory diseases.”

The study compared three oral inflammatory conditions:

• Peri-implantitis, inflammation and tissue breakdown around dental implants
• Chronic periodontitis, a more common form of gum disease around teeth
• Rapidly advancing periodontitis, a more aggressive form of gum disease marked by faster tissue destruction

The research findings

One of their major findings was that differences in bacterial burden alone did not explain why peri-implantitis and rapidly advancing periodontitis cause more severe tissue destruction. This suggested that changes in the body's own tissue response may play an important role in disease progression.

The key similarity they found was that CD38, a protein associated with inflammation, aging and cellular metabolism, was enriched in blood vessel cells in cases of rapidly progressing periodontitis and peri-implantitis.

By using spatial biology to compare these related diseases directly in human tissue, the team was able to identify a shared blood vessel pattern that may represent a drug-targetable mechanism of rapid tissue destruction.

“This hasn’t been described before in peri-implantitis,” said Easter, research scientist at the VCU School of Dentistry. “This is a new mechanism that could potentially change the way that this disease is thought about or even treated.”

What’s next?

Moving forward, the team plans to continue building single-cell and spatial atlases across more than 20 human diseases, including oral inflammatory diseases and cancer. By integrating these datasets, researchers aim to identify shared disease patterns, uncover potential therapeutic targets and support more precise approaches to treatment.

Collaborators