Experimental Study Of The Effect Of Insulin On The Response Of Osteoblast To Mechanical Stimulation

Background and objective:Orthodontic tooth movement is result from alveolar bone remodeling induced by mechanical strain, moving in a certain direction. Osteoblasts and osteoclasts are specialized cells responsible for this process. Bone remodeling is caused by osteoclast activity in the compression side and by the osteoblast-induced formation of new bone in the tension side.Type1diabetes mellitus, which is characterized by a lack of insulin production is associated with a decrease in skeletal mass, delayed healing of fractures, low bone-mineral density, osteoporosis and an increased prevalence and severity of periodontal disease. It accounts for5%to10%of diabetic patients and has a peak incidence at10to14years of age. With the development of economy, more and more people seek for orthodontic treatment. So it is inevitable that orthodontists will confront the patients with type1diabetes mellitus who seek for orthodontic treatment. The alteration of the metabolic state that interferes with bone remodeling can affect the tooth movement. Therefore, type1diabetes mellitus may affect alveolar bone remolding and the subsequent orthodontic tooth movement. But how the alveolar bone remolding in these people is still unclear. Since patients and orthodontists think more highly of delicate and individual orthodontic treatments, it is necessary to make clear the potential mechanism.Osteoblast is highly responsive to mechanical stimulus, and plays a leading role in bone remodeling. It not only plays important role in bone formation, but also mediates osteoclast differentiation and activation by producing receptor activator of nuclear factor KB ligand (RANKL) and osteoprotegerin (OPG). Investigating the role of insulin in regulating the response of osteoblast to mechanical stimulation may help us better understand the mechanism of alveolar bone remodeling during orthodontic tooth movement in the patients with type1diabetes mellitus. Method:MG63cells were subjected to mechanical strain by four-point bending system. Observed the effects of insulin on the mechanical strain-induced activation of extracellular signal-regulated kinase (ERK) and expression of cyclooxygenase-2(Cox-2) in MG63cells; Effects of insulin receptor antagonist or inhibitor of integrin function on the insulin-mediated effects on the mechanical strain-induced ERK phosphorylation and Cox-2expression; Effects of insulin on the mechanical strain-induced expressions of RANKL and OPG. Results:1,Insulin augmented tensile stress-induced ERK phosphorylation in a dose-dependent manner in MG63cells.2, Insulin augmented tensile stress-induced Cox-2mRNA expression through ERK pathway.3, S996and echistatin both inhibited the augmentation effects of insulin on tensile stress inductions of the activation of ERK and the expression of Cox-2.4, Insulin decreased tensile stress-induced RANKL and OPG mRNA expression and the ratio of OPG/RANKL.Implication:Insulin augments mechanical strain-induced Cox-2mRNA expression in MG-63cells through ERK pathway via integrins. Insulin regulates osteoclast differentiation via decreasing mechanical strain-induced RANKL and OPG mRNA expression and the ratio of OPG/RANKL in MG-63cells. These results imply that the sensibility of alveolar bone to mechanical stimulus weaken in the patients with type1diabetes mellitus because of the reduction in bone formation and bone resorption.