Experimental Study On The Effect Of Mandible Fracture On TMJ

As early as 1763, the importance of blood vessels in bone formation wasnoted: 'the origin of bone is the artery carrying the blood and in it the mineralelements' . Around the same time, Hunter suggested that blood vessels are keycontributors to the process of osteogenesis, both in development and duringrepair . During the following 200 years, studies of osteogenesis focused on therole of bone-forming osteoblasts, rather than on blood vessels. In 1963, Truetarevived interest in bone vasculature by publishing data that was based on yearsof bone studies. Trueta suggested the existence of a 'vascular stimulating factor(VSF)' operating at sites of bone damage .The idea of traditional medicine of our country is 'blood not flow ,bonenot joint'.So angiogenesis play a important role in the healing of bone fracture.As the most important factor,VEGF is essential for the healing of bone fracture.Angiogenesis is a very complicated course including the proliferation ofendothelium cell,the degradation of vascular basal membrane and extracellularmatrix, and the migration of the endothelium cell. VEGF affect various period ofangiogenesis directly or indirectly: through autocrine or paracrine, it conbinedwith the receptor at the vascular endothelium cell surface, by which it promotethe proliferation of endothelium cell and induce the neovascularity.The newvessels supply the bone fracture site with oxygen and nutriment, transportmetabolic waste and built a favourable microenvironment for localosteoanagenesis. Furthermore, osteoblast express Flt-1 with which VEGF bindto induce chemotaxis.Thus with the effect of VEGF, osteoblasts aggregate at thebone fracture site and differentiate. Then alkaline phosphatase was activated,calcium salts deposit and the healing of the bone fracture was facilitated.Inaddition,VEGF also promote the healing of the bone fracture by improve theblood supply to the surrounding soft tissue.A.B.M.Rabie,et al investigated the regulation mechanism of growth factorsin temporomandibular joint condyle growth, emphasized the direct or indirectand critical biological action of VEGF and illuminated the skeleton role ofcollagen X and II in the course of the condyle remodeling . Junko Aoyama ,et alobserved the expression of VEGF by the chondrocytes of the hypertrophic zoneduring postnatal development.The expression peaked on the tenth day andalmost can not be detected on the fortieth day. A.B.M.Rabie,et al tracted themandibular of mature rat forward and strong expression of VEGF was detectedin the chondrocytes of the hypertrophic and proliferative zone after 3 days.Theabove studies indicate that VEGF play a very important role in the remodelingof the temporomandibular joint.Based on the above studies ,we designed our experiment as follows:30 rabbits were divided into a control group and five experimental group atrandom and there are five in each group. The fracture models were made in themiddle of the left mandible of the rabbits with the multifunctional strikinginstallation and titanium small splints were used to fix the fracture site .Then thespecimens containing the fracture site and left temporomandibular joints weretaken after 48 hours and 1,3,5,8 weeks respectively. The histological changesof the fracture site and the temporomandibular joint of injured side wereobserved through eosin-haematoxylin staining and Chengku Li special staining.The expression of VEGF and Flt-1 at the fracture site and condyloid processwere detected by means of immunohistochemistry and in situ hybridization.Half quantitative analysis on VEGF staining was made by image analysis. Thenthe statistic analysis on gray scale integral value was made.Conclusions as followVEGF and its receptor Flt1 were expressed during mandibular fracturehealing, so VEGF appeared important biology effect to fracture healing. Duringfracture healing ,VEGF is expressed by cells including: osteoblasts,vascularendothelial cells,fibroblasts,mesenchymal stem cells and osteoclasts. On theone hand, VEGF can improve blood vessel's rebuilding through promotingvascular endothelial cells proliferation to step up bone fracture healing. One theother hand, VEGF educed synergetic biology effect wirh other growrhfactors(BMP,TGF,IGF,bFGF,PDGF,MMP and integrin) in osteoblasts,mesenchymal stem cells and osteoclasts. VEGF mRNA, VEGF and Flt-1receptor of VEGF were detected in many kinds of cells in the fracture siteduring 48 hours to 8 weeks after fracture, and high expression of VEGF and Flt1were detected from 1 week to 3 weeks after facture. Lesion of bilateraltemporomandibular joints were seen in all groups.VEGF and Flt1 receptor ofVEGF were detected in pillar cells of condyloid process in experimental groupsafter fracture. The expression of VEGF and Flt1 receptor run through theprocess of fracture healing, the maximal expressional period of them is from 1to 3 weeks, so VEGF is definitive and important in the process of blood vesselrebuilding after fracture. Mandibular fracture can induce lesion oftemporomandibular joints.VEGF and Flt1 maybe take part in healing aftertemporomandibular joints injury.So man-made recombinated VEGF has wide prospect in promotingmandibular healing and treating TMJ in clinical application .