Molecular mechanisms for bone resorption by gingipains: Degradation of osteoprotegerin by lysine-specific gingipain is a key factor for enhanced osteoclastogenesis

Oral Biosciences: The annual review 2014

“…Although the mechanisms by which gingipains cause bone resorption have not been elucidated in detail, it has been reported that a secreted form of the lysine-specific gingipain (Kgp) promotes differentiation of osteoclasts, which in turn facilitates bone resorption [68][69][70]. Miyamoto discussed the role of gingipains in alveolar bone loss during periodontitis in his review article, including his laboratory's recent findings that Kgp mediates proteolytic degradation of osteoprotegerin (OPG), a protein that inhibits osteoclastogenesis [71]. They found that osteoclast differentiation induced by active vitamin D 3 , Toll-like receptor (TLR) ligands such as lipopolysaccharide, and inflammatory cytokines such as tumor necrosis factor-α and interleukin-1β was enhanced by secreted Kgp in cocultures of mouse osteoblasts and bone marrow cells, whereas RgpB had no effect on osteoclast differentiation under the same experimental conditions.…”