Controlled Release of Osteoprotegerin: A Promising Supplementary Option for the Treatment of Apical Periodontitis with Large Periradicular Lesion

It often takes a relatively long period for a tooth with a large periradicular lesion to recover from bone destruction; therefore, it is necessary to develop additional approaches to serve as supplementary options to RCT. One possibility is to prevent the osteoclast-induced periapical bone destruction by inhibiting osteoclastogenesis. Recently, studies have proved the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system to be an important signal pathway regulating osteoclastogenesis, and inactivation of RANKL, which blocks the RANK/RANKL pathways, is critical in anti-bone resorption. The hypothesis: OPG, a natural decoy receptor for RANKL, may be a potential clinical anti-resorptive agent for apical periodontitis. Since OPG can block the RANK/RANKL pathways, it has been demonstrated to be a good candidate against bone destruction; its local delivery through root canals may be an additional option for treatment of apical periodontitis with large periradicular lesion.Evaluation of the hypothesis: OPG is easy to produce, store and use. Using a large animal study model, recombinant OPG could be incorporated into degradable carriers such as microspheres, micelle, and delivered into experimental induced periradicular lesions in the animals by controlled release, where it can relieve bone destruction by inhibiting osteoclastogenesis and osteoclast function. As OPG is a natural protein and clinical delivery as part of RCT treatment is easy and simple, the application of OPG may provide a new avenue for the treatment of apical periodontitis with large periradicular lesion.