Recent studies from the University of Pittsburgh suggest that manipulating the immune system may help in preventing or treating periodontal disease (PD), which is a widespread yet serious gum condition.
The research, featured in Proceedings of the National Academy of Sciences, demonstrated that administering microparticles containing the immune-regulating agent CCL2 directly into the gums could reduce bone loss and enhance bone healing in a mouse model of PD.
Senior author Charles Sfeir, D.D.S., Ph.D., an associate professor and chair of the Department of Periodontics and Preventive Dentistry at the Pitt School of Dental Medicine, explained, “Traditionally, PD treatments have focused on bacteria as the main culprit, but bacteria actually just trigger the disease by activating the immune response, which leads to inflammation and subsequent bone loss around the teeth. Our findings indicate that by managing the immune system, we can alter the bacterial environment to either prevent the onset of PD or halt its progression.”
Sfeir collaborated with Steven Little, Ph.D., a distinguished professor and chair of the Department of Chemical and Petroleum Engineering at the Swanson School of Engineering, who specialized in creating microparticles that can slowly release CCL2.
“The capacity for engineered systems to engage with the immune system within the periodontal area is remarkable and signifies a novel approach to treating diseases compared to current clinical methods,” Little remarked. “This partnership with Dr. Sfeir provides more evidence of the bright prospects for such innovative technologies.”
The research, led by first author Mostafa Shehabeldin, M.S., Ph.D., a former graduate student in Sfeir’s lab and now an assistant professor of periodontics at UT Health San Antonio, began by inducing PD in mice by tying a silk thread to one of their molars. The thread quickly gathered bacteria, causing inflammation and rapidly leading to bone destruction around the teeth within just four days.
To explore whether CCL2 could help prevent or treat the advancing PD, the researchers administered the microparticles either at the time of silk placement or four days later. They also assessed if CCL2 could assist in cases where the disease was naturally resolving by treating mice simultaneously with the removal of the silk.
In all three scenarios, CCL2 treatment was effective in either preventing or addressing PD by minimizing bone loss and promoting bone repair.
This positive impact was largely attributed to changes in macrophages, which are white blood cells that eliminate germs, clear dead cells, and stimulate other immune cells. In PD cases, many macrophages are of the inflammatory M1 type, but CCL2 treatment shifted them toward the anti-inflammatory M2 type.
The injection of microparticles also influenced the oral microbiome, helping to decrease or prevent increases in the overall bacterial load and the prevalence of certain bacteria species associated with PD.
“PD is a highly common inflammatory disease that affects many individuals in various degrees of severity,” noted Sfeir. “This research is promising because it may benefit a vast number of people.”
Sfeir hopes to test this new treatment method for PD in a future clinical trial. He predicts that CCL2 therapy would likely serve as an additional treatment option to complement existing bacterial-targeting methods, such as regular dental cleanings and antimicrobials.
“For 70 to 80 percent of individuals with PD, a dental cleaning is sufficient to eliminate inflammation,” Sfeir explained. “However, a small percentage of patients, despite receiving routine cleanings and maintaining thorough oral hygiene, continue to experience bone loss. For these aggressive cases of PD, effective therapies are still lacking, and we believe that immune modulation using agents like CCL2 could greatly assist in these situations.”
The results also provide valuable insights into the interactions between the immune system and the microbiome.
“The mouth is one of the few parts of the body where we can observe how microbes and the immune system interact, and it’s much easier to study than other areas like the gut or lungs,” Sfeir remarked. “This characteristic makes PD a crucial model for researching other immune-driven diseases.”
Additional authors involved in this study include Jin Gao, Ph.D., Yejin Cho, Rong Chong, M.S., Tracy Tabib, M.S., Sarah Gaffen, Ph.D., and Robert Lafyatis, M.D., all from Pitt; along with Lu Li, Ph.D., Matthew Smardz, and Patricia Diaz, Ph.D., D.D.S., from the University at Buffalo.
