Penn Dental prof fights back against gum disease

Nearly half of all adults have periodontitis, a gum disease associated with inflammation, bleeding, and, in its most severe form, destruction of the bone that supports teeth.

George Hajishengallis of the School of Dental Medicine has spent years studying the molecular mechanisms that lead to the disease. His recent research has found a way of stopping it by using a protein that can block both inflammation and bone loss in a two-pronged approach. The protein, Del-1, reduces inflammation by blocking the accumulation of neutrophils in gum tissue, which Hajishengallis had already known. That anti-inflammatory effect also stops bone loss to a degree. But now, it is clear that Del-1 also acts directly on osteoclasts, cells that absorb bone tissue, to slow their activity and maintain the teeth’s support structures. The work was published last month in Science Translational Medicine.

“This is not just important for periodontitis,” says Hajishengallis, the Thomas W. Evans Centennial Professor in Penn Dental Medicine’s Department of Microbiology. “It could also have implications for other inflammatory diseases where bone loss is involved.”

Together with members of his lab and researchers from Germany’s Technical University of Dresden, Hajishengallis examined various tissues in the body and found that Del-1 was expressed on osteoclasts, as well as some other tissues including the gums, brain, and liver.

That discovery, paired with experiments that suggested Del-1 was doing something more than inhibiting neutrophils to prevent bone loss in periodontitis, prompted the team to see whether the protein acted directly on osteoclasts.

Examining mice and cell lines lacking Del-1, they found that the protein appeared to slow down osteoclast formation. They also found one portion of the protein appeared to be responsible for the anti-osteoclast activity, while other regions played a bigger role in the anti-neutrophil effect.

Finally, and most important for translational use, in a preclinical model of periodontitis, the researchers showed that treating with Del-1 significantly reduced inflammation, tissue damage, and bone loss.

While the work raises hope for the millions of people with periodontitis, it could have an even broader reach if Del-1 could be used therapeutically to slow or stop bone loss associated with osteoporosis and rheumatoid arthritis, conditions that contribute to the mortality and disability of hundreds of millions of people around the globe. Those questions are being addressed in research that Hajishengallis and his colleagues have already begun.

Gum Disease