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Objective: To investigate the effect of adiponectin on the osteoblast differentiation and its signal transduction., Methods: Adipopnectin receptor (AdipoR) was detected by immunoblot analysis. Alkaline phosphatase (ALP) activity was measured by enzyme-linked immunosorbent assay. Osteocalcin was measured by a specific radioimmunoassay kit, and the extent of mineralized matrix was determined. RNA interference was used to down-regulate the expression of AdipoR1 in human osteoblasts, and the effect of adiponectin on osteoblast differentiation was investigated., Results: Only AdipoR1 protein was detected in human osteoblasts. Adiponectin could promote osteoblast differentiation, and result in a dose-dependent increase in ALP activity, osteocalcin secretion, and an increase in mineralized nodules. Suppression of AdipoR1 with siRNA could abolish the adiponectin induced ALP expression. Adiponectin could induce the activation of p38 and JNK, but not ERK1/2 in osteoblasts, and the pretreatment of osteoblasts with the p38 inhibitor (SB203580) could block the adiponectin-induced ALP activity., Conclusion: Adiponectin can induce human osteoblast differentiation via AdipoR1/p38 pathway.

Objective: To explore the variations of early-phase insulin secretion in Type 2 diabetic patients in different stages., Methods: L-arginine stimulative test, fast blood glucose and body mass index (BMI) were evaluated in 40 nomal controls (NC) and 101 Type 2 diabetic patients. The diabetic patients were divided into three groups: newly diagnosed group (n = 35), effectively treated by sulfonylureas group (n = 32) , and secondary failure of sulfonylureas group (n = 34). The indexs of insulin resistance of homeostasis model assessment (HOMA-IR), beta-cell insulin secretion of homeostasis model assessment (HOMA-IS), and the acute insulin response (AIRARG) index were calculated. Some statistical comparisons were done among the 4 groups., Results: The indexs of HOMA-IR in each group of Type 2 diabetic patients were all higher than those in NC group (P < 0.01). The AIRARG indexs were obviously lower in Type 2 diabetic patients in different stages than those in NC group (P < 0.01), and the subsequence from the highest to the lowest among the groups of diabetic patients was: the newly diagnosed group, the effectively treated by sulfonylureas group, and the secondary failure of sulfonylureas group (P < 0.01). But there was no significant difference in indexs of HOMA-IS between the newly diagnosed group and the effectively treated by sulfonylureas group., Conclusion: There is severe insulin resistance in Type 2 diabetic patients in each stage. The variations of early-phase insulin secretion manifest a vary procedure of obvious deterioration by degrees from the newly diagnosed group to the secondary failure of sulfonylureas group in Type 2 diabetic patients.

Objective: To prospectively investigate the relationship between high-sensitive C-reactive protein (hs-CRP) and Type 2 diabetic nephropathy., Methods: We assayed serum hs-CRP concentration in 55 normal controls, 66 Type 2 diabetic patients without diabetic nephropathy (DN) and 68 Type 2 diabetic patients with DN by ELISA. A 5-year prospective study was designed to investigate the changes of urinary albumin excretion (UAE), serum hs-CRP concentration, and kidney funciton in targeted intervention including blood glucose and blood pressure in 58 diabetic patients without DN at the baseline., Results: Baseline hs-CRP concentration was the highest in Type 2 diabetic patients with DN, followed by Type 2 diabetic patients without DN, and the lowest in normal controls. After 5-year intervention, hs-CRP concentration at the endline was significantly lower than that at the baseline in the patients in whom DN didn't occur at the endline (P < 0.05). But in the patients in whom DN occured at the endline, hs-CRP concentration was slightly lower than that at the baseline (P > 0.05). Both baseline and endline, the hs-CRP concentrations in the patients in whom DN occured at the endline were significantly higher than those without DN at the endline., Conclusion: Higher serum hs-CRP concentration in patients with Type 2 diabetes may be a risk factor that gives rise to DN. To some extent hs-CRP can predict the occurrence of DN in Type 2 diabetic patients.

Objective: To prospectively clarify the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and diabetic retinopathy (DR) in Type 2 diabetic patients., Methods: A 6-year prospectively study was designed to investigate the change of retina of 72 Type 2 diabetic patients without retinopathy . All patients suffered from diabetes mellitus for more than 5 years and matched well in age, body mass index (BMI), mean arterial pressure (MAP), and fasting blood glucose (FBG). Patients were classified into 3 groups according to their genotypes of ACE. ACE gene I/D polymorphism was identified by polymerase chain reaction. The patients were followed up for 6 years and their BMI, serum creatinine (Scr), MAP, HbA1c, and retina were checked once every 1 - 2 years., Results: Seven subjects (9.7%) were discontinued prematurely. At the end of the study, there were no significant differences in the clinical parameters such as BMI, MAP, FBG, HbA1c, and Scr among the 3 groups (P > 0.05), and also in DR incidence in Type 2 diabetic patients among the 3 groups (II 67.9%, ID 69.6%, DD 64.3%, respectively, P > 0. 05)., Conclusion: There is no association between ACE gene I/D polymorphism and the genesis and development of DR in Type 2 diabetic patients.

Objective: To investigate the direct effects of recombinant matrix metalloproteinase-14 (MMP-14) catalytic domain (RMC) on cultured human osteoblastic SaOS-2 cells., Methods: Western Blotting was used to analyze the expression of MMP-14 in cultured media. The effect of RMC on activation of proMMP-2 was measured by gelatin zymograms analysis, and the influence of RMC on cells adhesion was analyzed as well. The apoptosis was detected by acidine orange/ethidium bromide staining and ELISA., Results: RMC activated proMMP-2 secreted into media by SaOS-2 cells, and this process was blocked by EDTA treatment. RMC inhibited the adhesion of SaOS-2 cells to immobilized Type I collagen in a dose-dependent manner, which was also abolished by EDTA. RMC induced SaOS-2 cells apoptosis in a dose-dependent manner, and apoptosis-inducing activity of MMP-14 catalytic domain was blocked by EDTA., Conclusion: Since adhesion of cells to extracellular matrix serves as a survival mechanism in osteoblasts, the catalytic activity of recombinant MMP-14 catalytic domain on matrix proteins contributes to its apoptosis-inducing activity.