Regulation Of Bone Remodeling By Adiponectin Via Rankl/Opg Signaling During Orthodontic Tooth Movement

Objective Recently, adiponectin has emerged as an element in theregulation of bone metabolism, but the mechanism still remained to be explored,especially in the bone remodeling of orthodontic tooth movement. Thus,thepurpose of this study is to investigate the effects of local delivery of adiponectinsolution on bone modeling in the periodontal ligament during orthodontic toothmovement in rats. And to explore the possible regulatory mechanism of receptoractivator nuclear factor kappaB ligand(RANKL) and osteoprotegerin (OPG) inorthodontic tooth movement by injection the adiponectin at the sametime.Furthermore, we investigate the effects of adiponectin on the speed oforthodontic tooth movement and the number of osteoclast,so as to provide theadvance understanding of the molecular mechanisms of the bone remodelingand the theoretical basis for clinical orthodontic treatment.Methods An experimental model of orthodontic tooth movement wasestablished in adult Sprague-Dawley(SD）rats. Forty-five SD rats were randomlydivided into three groups, with fifteen in each group.The rats of group A werelocally injected with adiponectin in the buccal submucosal area of the first molar. whereas,the group B was injected with PBS and group C received no injections.The injections were applied every two days. The rats were sacrificed on days1，5，7，10and14. The distance of tooth movement was measured after sacrificed,selected tissue sections were stained with hematoxylin-eosin（HE）to observe thehistological morphologic alterations of the periodontal tissues and were stainedwith tartrate-resistant acid phosphatase(TRAP)histochemistry to analyze thechanges of the amount and distribution of osteoclasts. Immunohistochemicalstained was used for analysing of RANKL and OPG expression in theperiodontal ligament.The statistical analyses were performed using theSPSS16.0statistical program.Results(1) The distance of tooth movement: The distance of tooth movement wereincreased with the increased of experiment time.The distance of tooth movementin the group A was significantly lower compared with group B and group C onday7,10and14(P<0.01). But there was no obvious differences between GroupB and Group C (P>0.05).(2) TRAP-staining: The number of osteoclast on compression side allreached a peak on day7. There were no statistically significant on day1and3(p>0.05), while the number of osteoclasts in the group A was significantly lowercompared to the group B and group C on day7,10and14(P<0.05). Group Band group C didn,t show any significant differences.(3) Immumohistochemical staining:Compression site:The expression of RANKL and OPG on compression siteincreased at first, then decreased.The expression of RANKL in compression sitewas lower in group A compared with group B and group C.On the contrary, theexpression of OPG was significant higher in group A. Moreover, theRANKL/OPG ratio was decreased on compression site. The expression ofRANKL,OPG and the RANKL/OPG ratio are significant on day7,10and14(P <0.05).Tension side:OPG expression rose significantly on the tension sidecompered with group B and group C from day7(P <0.05). While RANKLexpression was lower than group B and group C, but the differences weresignificant only on day7(P <0.05). The RANKL/OPG ratio also significantlydecreased on tensile site on day7,10and14(P <0.05).Group B and group C didn,t show any significant differences.Conclusions Adiponectin can inhibit the expression of RANKL whilepromote the expression of OPG,and can significantly decreased RANKL/OPGratio.Consequently it reduce the number of osteoclasts in the compressing sideand slowdown the speed of orthodontic tooth movement. This study indicatethat adiponectin might be an inhibitor of bone remodeling in orthodontic.