The Effect Of Enhanced Masticatory Pressure On The Expression Of MMP-13 Of Rat Residual Ridge

Residual ridge resorption(RRR) has long been the focus of prosthodontic researches,which makes it difficult for the retention and stablity of complete denture.Many researchers had sutdied the pathological causes of RRR,and tried to prevent or even treat it.However,the conclusions were controversial due to the confusions in animal modeling and experimental designs.The stress condition of the alveolar bone has changed dramatically with the loss of teeth.If the chewing force exerted by the prosthetic appliance,such as complete denture,is far below the normal level,the disuse atrophy would developed.On the contrary,if chewing force is too large,it would accelerate a traumatic resorption through a mechanism which had not been understood throughly.RRR is a multifactorial process which involves many local and systemic factors,but the local stress is the most importment one.Controling the stress may serve as a way to resolve it also.Through the study of physiological and pathological mechanics of RRR,one could eliminate the traumatic influence of stress and reserve the alveolar,as well as control the pathological process in the bone from the genetic level.The sequelae of tooth extraction have been investigated in rats.These studies have shown that healing of extraction sockets and remodeling changes of the residual ridges were similar to those in humans,but the healing period was much shorter in rats than in humans.In rats the histological healing period of tooth extraction sockets was only two to four weeks.So in this study a rat traumatic RRR animal model has been developed.The change of the TRAP staining positive osteoclasts and MMP-13 expression level in the residual ridge has been investigated.The result shown the effect of MMP-13 in traumatic RRR,and the mechanism of traumatic RRR.50 healthy ten-week male Wistar rats were allotted into two groups at random:the experiment group and the control group.The left and right maxilla first molars were extracted.Then took impression in a custom impression tray after one month.The denture bases were made of the self-cured acrylic resin.The bite plane of the denture base was about 0.8mm over occlusal plane in the experiment group,and on the same to occlusal plane for the control one.50 rats were perfused and sacrificed after 3 days,7 days,14 days,28 days and 56 days. All the buccolingual sections in the first molar region were processed with HE staining,TRAP staining and MMP-13 immunohistochemistry(IHC) staining. Observing the histological changes of tissue and TRAP staining positive osteoclasts.The results of MMP-13 IHC staining were analyzed by the Computer Image Analyzing System.All the datas were treated by statistics test.The result showed that there was no significant histopathological change,no evidence inflammation,no bone resorption in the mucous of the control group,the number of TRAP staining positive osteoclast cells was little,and MMP-13 expression level was low,lying in the few of osteoblasts and fibroblasts.For the experiment group,on the 3rd day,there was no significant histopathological chang,On the 7th day and 14th day,the significant histopathological change was noted for the mucous of the alveolar.The epithelium and the lamina propria were severely compressed.Numbers of osteoclasts(OC) and Howshiop's lacunae were observed on the bone surface. Over the period from 28 day to 56 day,these histopathological change basically has not been seen.TRAP staining results of the the experiment group showed that:the number of TRAP staining positive OC was fewer on the 3rd day.On the 7th day,TRAP staining positive OC increased significantly.This phenomenon was most obvious in the bone surface.On the 14th day,there were a lot of TRAP staining positive OCs in the junction between mucosa and alveolar bone.Bone resorption lacunae were obvious.The number of TRAP staining positive OCs and TRAP staining positive particles reached the peak on the 14th day.The number of TRAP staining positive OCs substantial reduced on the 28th day,and basically returned to normal levels on the 56th day.It showed that OC activity was closely related to masticatory pressure loading on the alveolar ridge.The result of MMP-13 IHC staining of the experiment group showed that:on the 3rd day,compared with the control group,MMP-13 staining intensity increased slightly.On the 7th day,the MMP-13 level increased significantly and staining intensity markedly strengthened,and on the 14th day,MMP-13 level and staining intensity remained the same,but the number of osteoblast(OB)increased slightly.On the 28th day,the MMP-13 level decreased,and on the 56th day, compared with the control group,the MMP-13 level was no significant difference, which meaned the OC bone resorption activity slowed to stop.MMP-13 level,the amount of staining intensity and bone resorption process were consistent,and MMP-13 expression and the amount of staining intensity were related to the stress.In experiment group,the chewing force transmitted through the denture base to the alveolar is more than normal.The epithelial cells which are produced under the increased masticatory pressure have the potential deficits in the cell such as over-expression of death promoters and/or under-expression of death inhibitors, and then the lowered proliferative activity and accelerated cell death may lead to the thinner of epithelial thickness.The excessive masticatory pressure can lead to a series of biology reactions in the alveolar bone,OBs secrete MMP-13 to cleave intact collagen,the digested products of which may in turn activate OCs,which is the first step of bone resorption.Because the space between the base and the tissue was larger after RRR,so the masticatory pressure which was transmitted to alveolar ridge reduced in the later observation period,and OC differentiation and activation were inhibited through a series of signal transduction.Therefore,on 28th and 56th day,OC reduced and MMP-13 decreased,staining intensity reduced on alveolar surface.Within the limitation of this experiment,the results suggested that the denture base itself and the normal chewing force couldn't bring the pathological changes while the abnormal chewing force may cause the traumatic resorption of the alveolar bone.The fluctuation of the number of TRAP-positive OC,TRAP staining particles and MMP-13 level reflected the comprehensive bio-response caused by the pressure.The excessive force change the MMP-13 level and accelerate the RRR through the interaction of MMP-13 and OC.The MMP-13 played a key role in the development of RRR.The creativity of this study is that a rat traumatic RRR animal model has been developed,and the role of MMP-13 has been investigated in the residual ridge resorption for the firs ttime.The MMP-13 played a key role in the development of RRR..