Study On The Effects Of Nardosinone On Bone Metabolism And Its Mechanism

Apical periodontitis is a continuation of the endodontic space infection and it is manifested as a response of the host defense against the microbial action.It may determine local inflammation,hard tissue resorption,destruction of other periapical tissues.In this study,the effects of nardosinone(Nd)on bone were tested in a model of lipopolysaccharide(LPS)-induced alveolar bone loss,and the associated mechanisms were elucidated.Nd effectively suppressed LPSinduced alveolar bone loss and reduced osteoclast(OC)numbers in vivo.Nd suppressed receptor activator of nuclear factor-?B ligand(RANKL)-mediated OC differentiation,bone resorption,and F-actin ring formation in a dosedependent manner.Further investigation revealed that Nd inhibited osteoclastogenesis by suppressing the ERK and JNK signaling pathways,scavenging reactive oxygen species(ROS),and suppressing the activation of PLC?2 that consequently affects the expression and/or activity of the OCspecific transcription factors,c-Fos and nuclear factor of activated T-cells cytoplasmic 1(NFATc1).In addition,Nd significantly reduced the expression of OC-specific markers in mouse bone marrow-derived macrophages.Collectively,these findings suggest that Nd has beneficial effects on bone,and the suppression of OC number implies that the effect is exerted directly on osteoclastogenesis.