The Pathogenesis Of Diabetic Osteoporosis And The Effect Of Runx2and Osterix In Bone Formation

ObjectiveTo investigate the changes of bone metabolic markers and further discuss the pathogenesis of diabetic osteoporosis in order to prevent diabetic osteoporosis. To observe the expression of Runx2and Osterix mRNA and protein in type1diabetic rats, so as to provide theoretical evidence for the prevention and treatment of osteoporosis.Methods1. Model making and animal grouping:After one week’s adaptability breeding, fifty6-8week and average body weight (200±20) g female Wistar rats were randomly divided into experimental group (n=30) and control group (Group C, n=20). The type1diabetic rat models were established by injection of STZ60mg/kg intraperitoneally after a12-hour fast, then whether the rats have polyuria, polydipsia, polyphagia and sluggish were observed. The rats whose72h random blood glucose higher than16.7mmol/L were recruited.20of the models created were randomly chosen into the experiment and were regarded as diabetic model group (Group D).2. Index measuration:According to the need of experiment,5rats in each group were killed at1w,3w,5w,8w respectively, and samples were obtained for index measuration. The mRNA and protein expression of Runx2and Osterix in the right femur were detected by RT-PCR and Western-blot, respectively.Results23rats in experimental group met the standard. During the experiment, two diabetic rats died. The blood glucose level in Group D at each time point was significant higher than that in Group C (P<0.01). All rats gained substantial body weight, significant differences were found between the two groups (P<0.01), and body weight of rats in Group D declined firstly, then increased, and decreased again finally. RT-PCR tests showed that the expression of both Runx2and Osterix mRNA in Group D began to downregulate significantly since the1st week (P<0.01), and then regulated down significantly at the3rd,5th and8th week when compared to those in Group C (P<0.01). Western-blot tests showed that the expression of Runx2and Osterix protein in Group D began to decrease significantly since the3rd week (P<0.01), and then decreased significantly at the5th and8th week compared with those in Group C (P<0.01). The expression of Runx2and Osterix had a downward trend with the time prolonged.Conclusion1. The type1diabetic rats model, by injection of STZ60mg/kg intraperitoneally, characterized by high blood glucose and obvious diabetic syndromes. The model was established successfully.2. In the bone of diabetic osteoporosis rats, the expression of the mRNA and protein of the indices regulating osteoblast differentiation such as Runx2and Osterix, were significantly decreased, and bone formation reduced.3. The expression of Runx2and Osterix protein decreased since the3rd week, but the expression of Runx2and Osterix mRNA decreased since the1st week, so the1st week may be the key time to prevent osteoporosis.