Immune cells may damage teeth

The immune system may contribute to tooth loss associated with the gum disease periodontitis, according to a new study in the American Journal of Pathology. By comparing markers in diseased gum tissue samples to samples from healthy patients, the authors found that B-cells and T-cells in gum lesions were producing a key protein known to stimulate bone loss.

This paper "elevates the importance of lymphocytes in periodontal lesions," said Denis Kinane from the University of Louisville's School of Dentistry, who was not affiliated with the study.

Both gingivitis and periodontitis are characterized by inflamed gum tissue. In advanced periodontitis, however, the gums develop lesions that are packed with immune cells and can damage the bone that supports teeth. For approximately 30 years, scientists have struggled to identify the molecular basis for advanced periodontitis and the role immune cells play in pathogenesis. One protein, called RANKL (receptor activator of nuclear factor-KB ligand) may be a key player. Previous studies have suggested RANKL stimulates the differentiation and activation of osteoclasts, or cells that digest bone, in bone resorption diseases, such as osteoporosis and rheumatoid arthritis. Research has also shown RANKL is present in periodontal lesions.

"We just wanted to take the next step and see if we could connect the immune cells with RANKL," coauthor of the study Toshihisa Kawai of the Forsyth Institute told The Scientist. Using confocal microscopy, Kawai and his colleagues found that, among the many cell types identified in the lesions, only T-cells and B-cells expressed RANKL. In addition, ELISA assays showed RANKL is expressed mainly in diseased tissue samples, not healthy samples, adding further evidence that RANKL is a key player in pathogenesis. To test if the amount of RANKL was enough to cause cellular differentiation, the researchers performed an in vitro assay that demonstrated increased RANKL expression was sufficient to induce osteoclast differentiation.

Still, these findings do not show that RANKL triggers the bone resorption in advanced periodontitis, according to Thomas Van Dyke of Boston University, who was not involved with the study. "RANKL may be elevated from these cells, but many other molecules are elevated also," he told The Scientist in an Email. A subsequent experiment should interrupt the RANKL-pathway to prove that it is vital for periodontal bone resorption, Van Dyke noted.

Kinane said he is also "not truly 100% sure that [RANKL] is the most pivotal molecule" in the pathogenesis of periodontitis. Though it was a well argued and an interesting paper, he told The Scientist, more data are required to prove that RANKL is the key to bone loss in gum disease.

Kawai said he and his group are indeed planning to interrupt the RANKL pathway to confirm their hypothesis that RANKL is important for osteoclast activation and differentiation. These findings could also answer some outstanding questions, Kawai noted, such as why many lymphocytes are recruited to gum lesions.

Further experiments will also investigate the underlying difference between protein expression levels in healthy versus diseased tissues. "We just don't know how [periodontal disease] happens yet," Kawai said.

Juhi Yajnik
jyajnik@the-scientist.com

Links within this article:

T. Kawai et al., "B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease," Amer J Pathol, September 2006.
http://ajp.amjpathol.org/

Periodontitis Disease Information
http://www.mayoclinic.com/health/periodontitis/DS00369

Denis Kinane
http://www.louisville.edu/dental/research/kinane.htm

Tudor Toma, "Control of bone remodeling," The Scientist, April 22, 2002.
http://www.the-scientist.com/article/display/20343/

Y. Kong et al., "Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand," Nature, November 18, 1999.
PM_ID: 10580503

Steve Bunk, "Bone sculptor," The Scientist, May 15, 2000.
http://www.the-scientist.com/article/display/11861/

The Kawai Lab
http://www.forsyth.org/forsyth.asp?pg=100160

Thomas Van Dyke
http://www.creedd.org/vandyke.html

Laura Defrancesco, "The delicate balancing act," The Scientist, March 4, 2002.
http://www.the-scientist.com/article/display/12905/