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Background: Nucleolin (NCL) is the most abundant RNA-binding protein in the cell nucleolus and plays an important role in chromatin stability, ribosome assembly, ribosomal RNA maturation, ribosomal DNA transcription, nucleocytoplasmic transport, and regulation of RNA stability and translation efficiency. In addition to its anti-apoptotic properties, the underlying mechanisms associated with NCL-related roles in different cellular processes remain unclear. In this study, the effect of NCL on microRNA (miRNA) expression was evaluated by generating transgenic mice with myocardial overexpression of NCL and by analyzing microarrays of mature and precursor miRNAs from mice., Methods: Using microinjection of alpha-MyHc clone 26-NCL plasmids, we generated transgenic mice with myocardial overexpression of NCL firstly, and then mature and precursor miRNAs expression profiles were analyzed in NCL transgenic mice (n = 3) and wild-type (WT) mice (n = 3) by miRNA microarrays. Statistical Package for the Social Sciences version 16.0 software (SPSS, Inc., Chicago, IL, USA) was used to perform Student's t-test, and statistical significance was determined at P < 0.05., Results: Several miRNAs were found to be differentially expressed, of which 11 were upregulated and 4 were downregulated in transgenic mice with myocardial overexpression of NCL compared to those in WT mice. Several differentially expressed miRNAs were subsequently confirmed and quantified by real-time quantitative reverse transcription-polymerase chain reaction. Bioinformatics analysis was used for the prediction of miRNA targets. Furthermore, in vitro experiments showed that NCL regulated miR-21 expression following hydrogen peroxide preconditioning., Conclusions: Myocardial-protection mechanisms exerted by NCL might be mediated by the miRNAs identified in this study.

Background: Although various systemic and local factors such as abnormal carbohydrate or calcium metabolism, aging, and hormonal disturbances have been suggested as causes of ossification of the posterior longitudinal ligament (OPLL), the etiology of OPLL is not fully understood. The purpose of this study was to investigate whether bone morphogenetic protein (BMP)-2 is a candidate gene to modify the susceptibility of OPLL and the mechanism of signal transduction in ossification., Methods: A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. The complete coding sequence of the human BMP-2 gene was analyzed using polymerase chain reaction (PCR) and direct sequencing. All single nucleotide polymorphisms (SNPs) were detected and genotyped. BMP-2 expression vectors containing positive polymorphisms were constructed and transfected into the C3H10T1/2 cells. The expression of BMP-2 and the Smad signal pathway in positive cell clones were detected by Western blotting. The alkaline phosphatase (ALP) activity was determined using quantitative detection kits., Results: The frequencies for the 109T > G and 570A > T polymorphisms were different between the case and control groups. The "TG" genotype in 109T > G polymorphism is associated with the occurrence of OPLL, the frequency of the "G" allele is significantly higher in patients with OPLL than in control subjects (P < 0.001). The "AT" genotype in 570A > T polymorphism is associated with the occurrence of OPLL, the frequency of the "T" allele is significantly higher in patients with OPLL than in control subjects (P = 0.005). Western blotting analysis revealed that the expression of P-Smad1/5/8 protein transfected by wild-type or mutant expression vectors were significantly higher than control groups (P < 0.05), but there was no statistical difference in each experimental group (P > 0.05). The expression of Smad4 protein transfected by wild-type or mutant expression vectors was significantly higher than control groups (P < 0.05). The expression of Smad4 protein transfected by pcDNA3.1-BMP2 (109G) and pcDNA3.1-BMP2 (109G, 570T) was significantly higher than the other experimental groups (P < 0.05). The increase in ALP activity has been detected in pcDNA3.1-BMP2 (109G) and pcDNA3.1-BMP2 (109G, 570T) transfected cells up to 4 weeks after stable transfection. Activity of ALP was (30.56 ± 0.46) nmol×min(-1)×mg(-1) protein and (29.62 ± 0.68) nmol×min(-1)×mg(-1) protein, respectively. This was statistically different compared with the other experimental groups (P < 0.05)., Conclusions: BMP-2 is the predisposing gene of OPLL. The "TG" genotype in the 109T > G and the "AT" genotype in the 570A > T polymorphisms are associated with the occurrence of OPLL. The 109T > G polymorphism in exon-2 of the BMP-2 gene is positively associated with the level of Smad4 protein expression and the activity of ALP. The Smad mediated signaling pathway plays an important role during the pathological process of OPLL induced by SNPs of BMP-2 gene.

Background: The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells)., Methods: INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation., Results: The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone., Conclusions: Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.

Background: Steroid-induced osteonecrosis of the femoral head (ONFH) is a common clinical disease, with a high disability rate. At present, efficient prevention and treatment of steroid-induced ONFH is still lacking. The peroxisome proliferator-activated receptor-γ (PPARγ) is recognized as an important pathogenic gene for the development of steroid-induced ONFH. RNA interference (RNAi) is a tool for functional gene analysis, which has been successfully used to down-regulate the levels of specific target proteins. Therefore, down-regulation of PPARγ expression by RNAi may prevent the incidence of steroid-induced ONFH., Methods: According to the principles of siRNA design, three duplex siRNA sequences (971 - 989, 1253 - 1271 and 1367 - 1385) derived from the PPARγ gene (NM&#95;001082148) were synthesized. These duplexes were annealed, purified and ligated into 1.0-cytomegalovirus (CMV) shuttle vector. The shuttle vector was transfected into HEK293 cells. The HEK293 generated recombinant adenovirus vector carrying PPARγ siRNA sequences was purified and the titer of recombinant adenovirus was determined., Results: After the annealing of single-strand DNA oligo encoding short hairpin RNA (shRNA) sequences, products were identified by gel electrophoresis. These products were ligated into the 1.0-CMV shuttle vector and the recombinant shuttle vectors 1.0-CMV-971, 1.0-CMV-1253 and 1.0-CMV-1367 were constructed. These sequences of these recombinant vectors were confirmed. We then successfully constructed the recombinant adenovirus vector carrying siRNA targeting PPARγ. After purification, the virus titer was higher than 10(10) plaque forming unit (PFU)/ml., Conclusion: In this study, three recombinant adenovirus shuttle vectors carrying siRNA targeting PPARγ, including shuttle vectors 1.0-CMV-971, 1.0-CMV-1253 and 1.0-CMV-1367, were successfully constructed and high titers of recombinant adenovirus were obtained.

Background: Most of the basic and clinical studies of osteonecrosis of the femoral head (ONFH) are restricted to bone tissues only, whereas various systems are involved in the onset and development of ONFH, including nervous system. Peptidergic nerve participates in the neuronal regulation of bone metabolism and anabolism, and plays key roles in the growth, repair and reconstruction of bone. Calcitonin gene-related peptide (CGRP), which is secreted by peptidergic nerve, is the main mediator of bone metabolism. It dramatically promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Additionally, it enhances the osteoblast mass and the rate of osteoblast formation, and reduces the bone resorption by acting on osteoblasts and osteoclasts. Hence, we aimed to construct recombinant retrovirus vector pLNCX(2)-hCGRPα and to investigate the proliferation and osteogenic potential of hCGRPα-producing BMSCs (BMSCs/pLNCX(2)-hCGRPα) after virus infection., Methods: The constructed recombinant retrovirus vector pLNCX(2)-hCGRPα was transfected into PT67 packaging cells by lipofectamine 2000. Virus was collected for BMSCs infection. The mRNA and protein expression of hCGRPα was examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. The cell proliferation was determined by methyl thiazoleterazolium (MTT) assay. The osteogenic potential of BMSCs was evaluated by alkaline phosphatase (ALP) activity., Results: Both mRNA and protein expression of hCGRPα was detected in BMSCs/pLNCX(2)-hCGRPα cells. These cells exhibited significantly elevated proliferation and ALP value as compared with control BMSCs (P < 0.05)., Conclusion: BMSCs/pLNCX(2)-hCGRPα cells could stably express hCGRPα and showed promoted proliferation ability and osteogenic potential as compared with control BMSCs.

Background: Insulin resistance is an underlying feature of both type 2 diabetes and metabolic syndrome. Currently, it is unclear whether nuclear factor (NF)-κB inducing kinase (NIK) plays a role in the development of insulin resistance. The present in vivo study investigated the roles of NIK and IκB kinase α (IKKα) in obesity-induced insulin resistance using animal models., Methods: NIK expression was evaluated by Western blotting in male Lep(ob) mice and C57BL/6J mice fed a high-fat diet (HFD) (45% fat). After metformin and sulfasalazine treatment, NIK expression was investigated during the improvement of insulin resistance., Results: NIK was increased by about 1-fold in the renal tissues of Lep(ob) mice and C57BL/6J mice fed a HFD for 12 weeks. After 1 and 3 weeks of high-fat feeding, we observed an almost 50% decrease in NIK and IKKα expression in the liver and renal tissues of C57BL/6J mice. NIK expression was significantly lower in the liver and renal tissues of HFD-fed mice that were treated with insulin sensitizers, metformin and sulfasalazine. However, IKKα expression was increased after metformin treatment in both tissues., Conclusion: These results suggest a possible role of NIK in the liver and renal tissues of insulin-resistant mice.

Background: Pancreatic beta-cell apoptosis induced by lipotoxicity, to a large extent, contributes to the progression of type 2 diabetes. To investigate the mechanism of free fatty acid induced apoptosis, we aimed to study the effects of palmitic acid (PA) on the apoptosis and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression in βTC3 cells as well as the possible role of nuclear factor-κB (NF-κB) in this process., Methods: Hoechst 33258 was used to detect βTC3 cell apoptosis, which was induced by PA stimulation for 12 hours. PGC-1α expression was analyzed by reverse transcription polymerase chain reaction, IκB kinase β (IKKβ), IκBα, NF-κB-inducing kinase (NIK) and Rel-B expressions were analyzed by Western blotting. MG132 was employed to block the endogenous IκBα degradation before PA administration, and then its effect on PA-inducing cell apoptosis and PGC-1α mRNA expression was analyzed., Results: Significant increased cell apoptosis was found at the concentration of 0.5 mmol/L and 1.0 mmol/L PA administration. PA (0.5 mmol/L) could extensively reduced the expression of PGC-1α mRNA. After exposing βTC3 cells to 0.5 mmol/L PA for different time periods (0, 4, 6, 8, 10 and 12 hours), IKKβ protein expression increased while IκBα, NIK and Rel-B protein expression declined in a time-dependent manner. Pretreatment with MG132 to inhibit the degradation of IκBα, partially prevented the down-regulation of PGC-1α mRNA expression after 12-hour PA treatment in accordance with the decrease of PA induced apoptosis., Conclusions: NF-κB canonical pathway was activated in PA-mediated βTC3 cell apoptosis, whereas non-canonical pathway was inhibited. Reduced PGC-1α expression by PA in βTC3 cells could involve the activation of canonical NF-κB pathway, so as to deteriorate the PA induced apoptosis.

Background: Overwhelming evidences on chronic myeloid leukemia (CML) indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated., Methods: We have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Ph(+) patients with hemangioblast property. In this study, we isolated CML patient-derived Flk1(+)CD31(-)CD34(-) mesenchymal stem cells (MSCs) and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization (FISH) analysis, fluorescence activated cell sorting (FACS), enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors., Results: CML patient-derived Flk1(+)CD31(-)CD34(-) MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro., Conclusions: CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells (HSCs). MSCs might be a potential target for developing efficacious treatment for CML.

Background: Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve beta-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and beta-cell function and assess the variables predictive of long-term near-normoglycemic remission., Methods: Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion (CSII) and followed up longitudinally. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, hemoglobin A1c (HbA1c) and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group., Results: The duration to be diagnosed of the patients (from the time that patients began to have diabetic symptoms until diagnosis) in the remission group was shorter than that in the non-remission group (1.00 month vs 4.38 months, P = 0.040). The increase of the acute insulin response (AIR) was maintained after 2 years in the remission group compared with AIR measured immediately after intervention (413.05 pmol*L(-1)*min(-1) vs 408.99 pmol*L(-1)*min(-1), P = 0.820). While AIR in the non-remission group significantly declined (74.71 pmol*L(-1)*min(-1) vs 335.64 pmol*L(-1)*min(-1), P = 0.030). Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio (OR) 1.019, P = 0.038, while fasting plasma glucose (FPG) and post-breakfast plasma glucose (PPG) after CSII were the risk factors (OR 1.397, P = 0.024 and OR 1.187, P = 0.035, respectively)., Conclusion: The near-normoglycemic remission is closely associated with long-term maintenance of beta-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.

Background: The usefulness of in-phase/opposed-phase imaging and diffusion weighted imaging (DWI) in differentiating benign and neoplastic vertebral fractures has been described. In this study, we aimed to evaluate the influence of the severity of vertebral damage on the diagnostic performance of these two technologies., Methods: Totally 59 patients with 68 acute benign vertebral fractures and 43 patients with 79 vertebral metastases were included in this study. The MR protocol included DWIs and sagittal in-phase/opposed-phase gradient recalled sequence. The severity of vertebral damage was expressed by lesion ratio (LR, the ratio of lesion area to vertebral area on the slices of largest abnormal signal area in the T1-weighted sequence). Quantitative (signal intensity ratio (SIR) defined as signal intensity (SI) on opposed-phase gradient recalled echo (GRE) images divided by SI on in-phase; apparent diffusion coefficient (ADC) value derived from DWI analysis was performed, the relationships between LR and the measurements of these two technologies were analyzed using linear regression. The covariate-specific receiver operating characteristic (ROC) curves were also fitted to evaluate the influence of LR on the diagnostic performance of ADC and SIR., Results: The difference in both SIR and ADC for vertebral metastasis and acute benign vertebral fractures was significant (P < 0.001). A positive correlation between the LR and the SIR was found in benign fractures (P < 0.05). The severity of vertebral damage had a significant influence on the AUC (area under ROC curve) for SIR (P < 0.05) but ADC (P > 0.05). More severe cases were associated with increased AUC for SIR., Conclusions: LR is capable of affecting the diagnostic performances of chemical shift imaging. Thus, when applying these tests to make diagnoses on vertebral fractures, the severity of the vertebral damage should be taken into account. The covariate-specific ROC model is recommended because it substantially improves the ability to avoid bias when evaluating tests.

Background: Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China., Methods: Inadequate glycaemic control in diabetic patients was defined as HbA1c = 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents (OA), insulin plus OA (insulin + OA), or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy., Results: Among 493 diabetic inpatients with known history, 75% had HbA1c = 6.5%. Inadequate glucose control rates were more frequently seen in patients on insulin + OA regimen (97%) than on OA regimen (71%) (P < 0.001), and more frequent in patients on combination therapy (81% - 96%) than monotherapy (75%) (P < 0.05). Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI (P < 0.01)., Conclusions: This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed. It is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.

Background: Many patients with acute coronary syndrome (ACS) develop recurrent angina (RA) during hospitalization. The aim of this non-randomized, prospective study was to investigate the predictive factors of RA in unselected patients with ACS enrolled in the global registry acute coronary events (GRACE) during hospitalization in China., Methods: Between March 2001 and October 2004, enrolled were 1433 patients with ACS, including ST segment elevation myocardial infarction (662, 46.2%), non-ST segment elevation myocardial infarction (239, 16.7%) and unstable angina (532, 37.1%). The demographic distribution, medical history and clinical data were collected to investigate the predictive factors of RA by Logistic regression., Results: During hospitalization 275 (19.2%) patients were documented with RA including unstable angina (53.2%), non-ST segment elevation myocardial infarction (27.5%), ST segment elevation myocardial infarction (19.3%). A comorbidity of dyslipidemia, prior angina, percutaneous coronary intervention (PCI) within 6 months was more common in patients with RA, P < 0.05. In the patients with RA, a significantly higher proportion of patients with acute pulmonary edema was observed, 23 (8.4%) versus 43 (3.7%), P = 0.001. Acute renal failure was present in 8 (2.9%) of patients with RA versus 19 (1.6%) of patients without RA, P = 0.165. Hemorrhagic events were present in 6 (2.2%) of patients with RA versus 8 (0.7%) of patients without RA, ventricular tachycardia/ventricular fibrillation events in 12 patients (4.3%) versus 22 patients (1.9%), congestive heart failure in 69 patients (25.0%) versus 94 patients (8.1%), myocardial re-infarction in 28 patients (10.1%) versus 15 patients (1.3%), P < 0.05, respectively. A lower proportion of patients with RA underwent in-hospital PCI, 687 (59.3%) versus 114 (41.5%), P = 0.000. A higher proportion of patients with RA received heparin, 260 (94.5%) versus 1035 (89.4%), P = 0.006; and beta-blockers 176 (64.0%) versus 864 (74.5%), P = 0.000. Multivarible regression analysis showed that RA was associated with prior angina (OR 2.086, 95% CI 1.466 - 2.967), in-hospital PCI (OR 0.579, 95% CI 0.431 - 0.778), in-hospital congestive heart failure (OR 2.410, 95% CI 1.634 - 3.555), myocardial re-infarction (OR 7.695, 95% CI 3.701 - 15.999), beta-blocker (OR 0.626, 95% CI 0.458 - 0.855), and heparin (OR 3.411, 95% CI 1.604 - 7.382)., Conclusions: In-hospital congestive heart failure, myocardial re-infarction, prior angina history and use of heparin are stronger independent predictors of RA; beta-blockers and PCI are also important predictive factors for RA.

Background: Vitrification is a prospective technology in ovarian tissue cryopreservation, but it is still in an initial stage. This study was conducted to investigate a modified vitrification protocol for human ovarian tissue, which can be used as an alternative to preserve fertility for young women with cancer who have to undergo cytotoxic therapy and sterilization., Methods: Ovarian tissue samples were collected from 15 patients and randomly allocated to groups of fresh, vitrification, and conventional slow freezing. A modified carrierless vitrification method was applied. The proportion of morphologically intact follicles in fresh ovarian tissues was compared with that in warmed/thawed tissues. The initial growth of the follicles and the concentrations of estradiol and progesterone were detected to determine the viability and endocrine function of the cryopreserved tissues., Results: The proportion of morphologically intact primordial follicles in the fresh group (97.6%) was significantly higher than that in the other two groups (vitrification group 80.3% and slow-freezing group 72.6%, P < 0.001). In both the vitrification and slow-freezing groups, estradiol and progesterone were secreted continuously during 2-week culture in vitro, the proportion of primary follicles were both significantly increased compared to the fresh group. No statistically significant differences existed between the two groups after cryopreservation in the proportion of both primordial and primary follicles, and the concentrations of estradiol and progesterone (P > 0.05)., Conclusion: The modified vitrification method for cryopreservation of human ovarian tissues is effective, simple, and inexpensive.

Background: In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone (Dex) on differentiation of marrow stromal cells (MSCs), and to investigate the pathobiological mechanism of steroid-induced osteonecrosis., Methods: MSCs in cultures were treated with increasing concentrations of Dex (0, 10(-9), 10(-8), 10(-7), and 10(-6) mol/L) continuously for 21 days. The cells, which were exposed to 0 mol/L (control) or 10(-7) mol/L Dex for 4 - 21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan III. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase (ALP) of MSCs treated with 0, 10(-8), 10(-7), and 10(-6) mol/L Dex for 12 days, and that treated with 0 mol/L and 10(-7) mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10(-7) mol/L Dex were detected. The mRNA expression levels of adipose-specific 422 (aP2) gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10(-7) mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student's t test and analysis of variance. P values less than 0.05 were considered significant statistically., Results: The number of adipocytes in cultures increased with the duration of MSCs' exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10(-7) mol/L Dex group on day 12 (t = 20.51, P < 0.001). The level of triglycerides in 10(-7) mol/L Dex group was 3.40 times of that in the control (t = 11.00, P < 0.001). The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10(-7) mol/L Dex group respectively. As compared to the control, the mRNA expression of adipose-specific 422 (aP2) gene in 10(-7) mol/L Dex group was significantly increased (t = 36.48, P < 0.001), and that of osteogenic gene type I collagen was decreased (t = 42.07, P < 0.001)., Conclusions: Dex can directly induce the differentiation of MSCs into a large number of adipocytes and inhibit their osteogenic differentiation, which provide a novel explanation for the pathologic changes of steroid-induced osteonecrosis.