Double-stranded RNA provoke bone loss during periodontitis

Researchers from Tokyo University of Agriculture and Technology have made a novel revelation about the processes of bone loss in gum disease (periodontitis). They discovered that double-stranded RNA molecules can stimulate the immune system, causing bone degeneration.

Their study was published in the Journal of Biological Chemistry in March.

Serious gum infections impact negatively on the soft tissues of the mouth, including the gums, as well as the underlying (alveolar) bones that hold our teeth. Bacterial infection has the potential to break down both the bone pockets surrounding the base of teeth and the ligaments that bind teeth to the jawbone. If left uncontrolled, periodontal bone erosion might eventually lead to tooth loss.

Periodontal disease is caused by bacterial plaque concentrations buried in the tooth pockets, which has been known for a long time. Lipopolysaccharides are the major components of the outer membranes of bacteria causing gum disease.

Lipopolysaccharides not only maintain the bacterial cell and protect it from immune cell attack, but they have also been linked to gum inflammation by activating toll-like receptors (TLR4) on immune cells, which subsequently perceive the bacteria as pathogens and cause inflammation.

Moreover, until now it was uncertain whether “other pathogens including double-stranded RNA (dsRNA) derived from bacteria or autologous cells contribute to the progression of periodontal bone loss,” explains study author and Professor Masaki Inada, D.D.Sc and PhD in the Department of Biotechnology and Life Science.

Immune cells such as neutrophils that have collected in inflammatory tissues, for instance, may produce dsRNA in the mouth. The role of dsRNA in the advancement of bone inflammation during periodontal disease was explored in a latest study.

In healthy bones, stromal osteoblasts on the bone’s outer surface set down new bone material, while osteoclasts derived from hematopoietic cells tear down old bone for mineral outflow—however, the balance among their activities maintains bone mass.

RANKL, a protein, is involved in maintaining that balance and, as a result, in how bone is properly reconstructed. RANKL is upregulated during gum inflammation by the hormone-like PGE2 (prostaglandin E2) molecule, which is found naturally by osteoblasts. Changes in PGE2 production, and hence RANKL, would have an impact on bone loss and gain.

The researchers used osteoblasts and bone marrow cells from mice, as well as a synthetic chemical that mimicked dsRNA, to test if the cells might be exposed to dsRNA. They discovered that the dsRNA triggered the differentiation of additional osteoclasts, or bone-breaking cells. The dsRNA induced osteoblasts to create more of the hormone-like PGE2, which increased RANKL levels and encouraged differentiation in osteoclasts.

As a result of their connections with the dsRNA molecules, the osteoblasts communicated biological signals to the bone-eroding osteoclasts, which increased their output. In addition, the dsRNA made adult osteoclasts live longer.

When gums are inflamed from bacterial illness, more, longer-surviving osteoclasts lead to more bone adsorption. Gum disease induces bone deterioration in a previously undiscovered method, according to the study.

These data suggest that TLR3 signalling in stromal osteoblast controls PGE2 production and induces the subsequent differentiation and survival of mature osteoclasts.

Masaki Inada, Professor and Study Author, Biotechnology and Life Science, Tokyo University of Agriculture and Technology

The stromal osteoclasts cause inflammatory resorption of the teeth-supporting bones. Knowing that dsRNA delivered via bacteria or an accumulation of immune cells in tissues can trigger inflammation leading to bone destruction in periodontitis is a significant step forward in combating the disease’s impacts.

The researchers want to investigate how dsRNA contributes to periodontitis progression over time by triggering immune system receptors on stromal osteoblasts to produce more PGE2. The foundation for developing new treatment to prevent bone loss from gum disease is studying the mechanisms involved.