Study Of The Mechanisms On The Modification Of Extracellular Matrix During Orthodontic Periodontal Tissue Remodelling

Periodontal tissue remodeling during orthodontic tooth movement result from the cellular biological responses of connective tissue to exogenous mechanical forces. Among these responses, the degradation and synthesis of extracellular matrix (ECM) take place. But, the identification of the molecular basis as well as the mechanisms on the modification of ECM in these processes are poorly understood. Previous studies indicate that matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) system played a key role in ECM metabolism. Dynamic equilibrium of MMPs and TIMPs makes it possible to keep normal tissue remodelling physiologically, that is at least in part regulated by local cytokines. MIMP-3 (Stromelysin-l), one prominent member of the family of MMPs, can not only degrade solely the most components of ECM, but also can activate MMP-l, MMP-8 and MMP-9. The regulation of their activation by MMP-3 may be important in the overall regulation of the connective tissue degradation in both physiologic and pathologic conditions. Thus, this study centers on the effects of mechanical forces and interleukin-6 (IL-6) on the expression of MMP-3 by periodontal ligament cells and osteoclasts in vivo and in vitro, to elucidate the mechanisms on the metabolism of ECM associated with tooth movement and enhance our understanding of the biological mechanisms involved in tissue remodelling that occurs during orthodontic treatment. .5. This study mainly contains the following works: 1: The expression of MMP-3 and TIMP-1 during orthodontic tooth movement in rats. Objective: To observe the change of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase- 1 (TIMP- 1) expression during experimental tooth movement in rats ,learn about the relationship between MMP-3, TIMP-l and orthodontic periodontal tissue remodeling. Methods: Orthodontic appliance was placed between the maxillary right first molar and maxillary central incisors of adult SD rat. Established rat molar movement model. Immunohistochemistry and image analyses were performed at 1-. 3?5~. 7~. 14 days after orthodontic force application Results: The expression of MMP-3 and TIMP-l were weak immunopostive in normal periodotium. At ld after tooth movement, the immunoreactivities of MMP-3 were increased, at 5d , reached the maximum. Osteoclasts were also observed strong positive. The expression of TIIvIP- 1 was increased at 3 days. At 7 days, a marked increase in TIMP- I -positive firblasts and osteoblasts was found not only on the pressue side but also on the tension side of the periodontium. Conclusion: MMP-3 and TIMP-l participate in orthodontic periodontal tissue remodeling during tooth movement MMP-3 may play an important role in osteoclastic bone resorption. 2:Effects of cyclic-tension force on the expression of MMP-3 and TIMP-1 by human periodontal ligament celis. Objective: To investigate the effects of the mechanical stretching on the expression of MMP-3 and TIMP- I in human periodontal ligament cells (HPDLC), and to unveil the molecular mechanism of ECM metabolism during orthodontic periodontal tissue remodeling. Methods: HPDLC were subjected to 12% elongation by strain unit at 6cycles/min (i.e. 5-s elongation and 5-s relaxation) for 1, 3and 5days in this experiment. Expression and secretion of .6.