Anti-mouse RANKL Antibodies Inhibit Alveolar Bone Destruction in Periodontitis Model Mice

Abstract

Denosumab is an anti-bone resorptive drug consisting of complete human monoclonal antibodies that targets receptor activator of nuclear factor κB ligand (RANKL), which is responsible for osteoclast formation. The drug has been adapted for bone diseases, such as osteoporosis and bone metastasis related to cancer, but is not used for alveolar bone destruction related to periodontitis. In the present study, we aimed to clarify whether denosumab prevents bone destruction associated with lipopolysaccharide (LPS)-induced calvaria inflammation and experimental periodontitis in model mice. Denosumab does not bind to mouse RANKL, thus we used anti-mouse monoclonal RANKL antibodies. We also examined the inhibitory effects toward bone destruction of another anti-bone resorptive drug zoledronate, a nitrogen-containing bisphosphonate. Local administration of anti- RANKL antibodies into the calvaria area inhibited LPS-induced osteoclast formation and bone destruction, while zoledronate inhibited bone destruction but not osteoclast formation due to its different action mechanism. In periodontitis model mice, in which the second molars were ligated with a silk suture to induce inflammation, intraperitoneal administration of anti-RANKL antibodies significantly inhibited alveolar bone destruction and tooth root exposure. On the other hand, zoledronate only weakly repressed alveolar bone destruction and failed to inhibit root exposure. These results suggest that denosumab is a promising candidate to prevent alveolar bone destruction associated with periodontitis.

Glycemic fluctuation exacerbates inflammation and bone loss and alters microbiota profile around implants in diabetic mice with experimental peri-implantitis

“…Long-lasting hyperglycemia also promotes the proliferation and differentiation of osteoclasts, resulting in bone tissue more susceptible to resorption [ 31 , 32 ]. RANKL Ab and miR146a have been proven to negatively modulate inflammatory responses in the periodontium or periodontal cells [ 33 , 34 ]. Local RANKL Ab or miR146a administration can inhibit osteoclast formation and reduce bone destruction in inflammatory diseases [ 34 , 35 ].…”

A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction

“…These classical pro-inflammatory markers of periodontitis present potential therapeutic target for periodontitis treatment 50 , 51 . In this regard, several studies demonstrated that pharmacological treatments, including the use of synthetic drugs and natural compounds, such as TNF-α antagonist 52 , angiotensin II receptor blocker 53 , non-selective β-blocker 54 or anti-RANKL antibodies 55 , resulted in reduced levels of TNF-α, NF-κB and RANKL, thereby, resolving experimental periodontitis in vivo . The use of such aforementioned conventional pharmacological drugs in periodontal therapy is not devoid of side effects, thus, necessitating the development of novel therapeutic agents and strategies to provide safer alternatives.…”

Effects of lipid metabolism on mouse incisor dentinogenesis

“…2; MINITOR CO., Ltd. Tokyo, Japan), standard rotary (M212H; MINITOR CO., Ltd. Tokyo, Japan), and 1-mm round bur, with the mice given the same mixed anesthetic noted above. Tooth elongation process X-ray photography was performed with an in vivo μCT system (R_mCT2; Rigaku Co., Ltd., Tokyo, Japan) at 1 and 2 weeks after defacement 51 . Incisor elongation rate was determined by measuring from the alveolar bone crest to middle of the round lesion using the Image J software package, version 1.52a (National Institutes of Health, Maryland, United States).…”