A New Weapon Awaits Periodontitis

Switching off a single master protein may usher a dramatic shift in how dental professionals treat periodontitis, and researchers who discovered how the manipulation of this protein affects bone loss are calling for a potential new focus of treatments for both periodontitis and osteoporosis.

The door to this potential change in periodontitis treatment swings open as a result of collaborative research efforts at University of California, Los Angeles (UCLA), the University of Michigan and the University of California, San Diego. The group’s study appears in the May 17 online edition of the journal Nature Medicine.

At the centerpiece of the research led by UCLA’s Cun-Yu Wang, DDS, PhD, is achieving the prevention of bone loss by maintaining bone formation, a process the study suggests may be accomplished by inhibiting nuclear factor-kB (NF-kB), a master protein that controls genes associated with inflammation and immunity.

Transforming these findings into a successful form of treatment could change the landscape for millions who are affected with periodontitis and osteoporosis each year.

Mild to moderate periodontitis affects a majority of adults in the United States, and 5% to 20% of the nation’s population suffers a more severe stage of the disease, according to the American Academy of Periodontology.

The NF-kB protein, a contributor in inflammatory and immune disorders, plays a major role in both osteoporosis and periodontitis, disrupting the healthy balance of bone destruction and formation. It is this balance that Wang and his fellow scientists seek to restore, and perhaps even improve upon, by finding new ways to promote net bone accumulation.

“Most studies focus on the part that NF-kB plays in the regulation of osteoclasts—bone-resorbing cells. For the past 5 years, we looked closely at the effect of NF-kB on osteoblasts—bone-forming cells,” says Wang, who holds UCLA’s No-Hee Park Endowed Chair in the Dental School’s Division of Oral Biology and Medicine.

“We knew that NF-kB promoted bone resorption. What we discovered in our in vitro and in vivo studies is that this protein also inhibits new bone formation, giving us a fuller picture of its role in inflammation and immune responses,” Wang says.

Many currently available treatments work to prevent further bone loss but are not able to increase bone mass. Wang’s research results reportedly support the idea that a new drug that prevents the action of NF-kB in cells may represent a major therapeutic advance.

“Although it has been known for some time that inflammation inhibits bone formation, the groundbreaking work by Dr. Wang and his colleagues elucidates the critical role of NF-kB in the mechanism that underlies this phenomenon,” says Philip Stashenko, DMD, PhD, a professor at the Harvard School of Dental Medicine and president and CEO of the Forsyth Institute, the preeminent research institution. “Many drugs that block NF-kB are in development, and these findings suggest that new treatments to preserve bone in periodontitis, osteoporosis, and related bone diseases are imminent.”

As a next step, Wang and his research team are planning to test small molecules that inhibit the specific bone-resorption and bone-inhibition actions of NF-kB in periodontitis and osteoporosis.

The study was supported by grants from the National Institute of Dental and Craniofacial Research and the National Institute of Diabetes and Digestive and Kidney Diseases.

Source: UCLA