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The formation characteristics of the shaped charge jet (SCJ) from the shaped charge with a trapezoid cross-section is analyzed in this work. A theoretical model was developed to analyze the collapsing mechanism of the liner driven by the charge with a trapezoid cross-section. Based on the theoretical model, the axial and radial velocities of the SCJ from different trapezoid cross-section charges. The pressure model was employed to calculate the velocity for the subcaliber shaped charge, which was verified through numerical simulation. The results show that the influence of the angle of the trapezoidal charge (acute angle) on the axial velocity of the SCJ is not distinct, whereas the variation of the radial velocity of the shaped charge jet is obvious as the change in the angle of the trapezoidal charge. In addition, the related X-ray experiments were conducted to verify the theory. The theoretical results correlate with the experimental results reasonably well.

Obese women often have certain degree of reproductive dysfunction with infertility. Although the clinical impact of obesity on female infertility has been extensively studied, the effective and targeted treatment is still lacking. Melanocortin-4-receptor knock-out (MC4R KO) mouse is an over-eating obese model with hyperphagia, hyperinsulinemia, reduced growth hormone (GH), and insulin resistance. Dapagliflozin improved the metabolic and hormonal parameters in MC4R KO mice. MC4R KO female mice were treated with dapagliflozin for 14 weeks from 14-week age. Age-matched WT littermates and non-treated MC4R KO mice were used as control groups. Food intake was measured daily. Body weight was measured twice a week. Estrous cycles, GH, and luteinizing hormone (LH) profiles were measured. Selected tissues were collected at the end of experiments for gene expression profiles and hematoxylin–eosin staining. Regularity and mode of hormonal profiles were restored by the dapagliflozin treatment. Estrous cycle was partially normalized, number of CL was significantly increased, and the expression of Kiss1 and Gnrh1 in the hypothalamus and LH in the pituitary was markedly increased by the dapagliflozin treatment. It is conclsuded that dapagliflozin may recover LH and GH profiles partially through modification of relevant gene expression in the hypothalamus and pituitary, and result in an improved ovulation rate in obese mouse model. Dapagliflozin may therefore improve fertility in obese patients.

Clinical studies have reported that miRNAs abnormal expression are associated with the generation of cisplatin-resistant to osteosarcoma. Our previous research found that miR-203 is downregulated in osteosarcoma cells and overexpressed miR-203 exerts antitumor properties on osteosarcoma cells. However, the role and mechanism of miR-203 in regulating the sensitivity of cisplatin in osteosarcoma cells remains unclear. This study aimed to investigate the effects of miR-203 in cisplatin therapy for osteosarcoma cells in vitro and determined the underlying mechanism. In this study, we found that miR-203 was significantly upregulated in osteosarcoma cells after exposure to cisplatin. miR-203 knockdown reduced the sensitivity of osteosarcoma cells to cisplatin by suppressing cell apoptosis, cell cycle arrest, and inducing invasion. Meanwhile, we found that miR-203 knockdown reduces the therapeutic sensitivity of osteosarcoma cells by upregulating RUNX2. Moreover, we found that RUNX2 silencing sensitizes osteosarcoma cells to chemotherapy treatment of cisplatin. In summary, our findings demonstrated that miR-203 knockdown reduces cisplatin chemo-sensitivity to osteosarcoma cells in vitro by targeting RUNX2, and speculated that miR-203 may be a target for drug resistance of osteosarcoma to cisplatin.

Background: Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone insulin-growth hormone (GH) balance has recently been proposed to maintain metabolism profiles. Time-restricted feeding (TRF) is an effective strategy against obesity without detailed research on pulsatile GH releasing patterns. Methods: TRF was performed in an over-eating melanocortin 4 receptor-knockout (MC4RKO) obese mouse model using normal food. Body weight and food intake were measured. Series of blood samples were collected for 6-h pulsatile GH profile, glucose tolerance test, and insulin tolerance test at 5, 8, and 9 weeks of TRF, respectively. Indirect calorimetric recordings were performed by the Phenomaster system at 6 weeks for 1 week, and body composition was measured by nuclear magnetic resonance spectroscopy (NMR). Substrate- and energy metabolism-related gene expressions were measured in terminal liver and subcutaneous white adipose tissues. Results: TRF increased pulsatile GH secretion in dark phase and suppressed hyperinsulinemia in MC4RKO obese mice to reach a reduced insulin/GH ratio. This was accompanied by the improvement in insulin sensitivity, metabolic flexibility, glucose tolerance, and decreased glucose fluctuation, together with appropriate modification of gene expression involved in substrate metabolism and adipose tissue browning. NMR measurement showed that TRF decreased fat mass but increased lean mass. Indirect calorimeter recording indicated that TRF decreased the respiratory exchange ratio (RER) reflecting consumption of more fatty acid in energy production in light phase and increased the oxygen consumption during activities in dark phase. Conclusions: TRF effectively decreases hyperinsulinemia and restores pulsatile GH secretion in the overeating obese mice with significant improvement in substrate and energy metabolism and body composition without reducing total caloric intake.

The penetration characteristic of a following kinetic energy projectile to the concrete with a pre-drilled cavity is investigated through the theory and numerical simulations. With the precondition of the equivalent volume of the pre-drilled cavity, the results are compared in terms of the kinetic parameters of the penetration process, the depth of penetration of the following kinetic energy projectile. A theoretical model is then employed to assess the depth of penetration of the following kinetic energy projectile at the condition of variation of the diameter and the depth but the volume of the pre-drilled cavity being invariant. In addition, the numerical simulation is carried out to present the penetration process of the following kinetic energy projectile to the concrete with a pre-drilled cavity. The results show that the existence of the pre-drilled cavity is conducive to increase the depth of penetration of the following kinetic energy projectile on the concrete. In case of the same volume of the pre-drilled cavity, the depth of penetration of the following kinetic energy projectile on concreter increases initially and decreases afterwards with increase of the diameter of the pre-drilled cavity. The theoretical results correlate with the simulation results reasonably well.

Disruption of endocrine hormonal balance (i.e., increased levels of insulin, and reduced levels of growth hormone, GH) often occurs in pre-obesity and obesity. Using distinct intracellular signaling pathways to control cell and body metabolism, GH and insulin also regulate each other's secretion to maintain overall metabolic homeostasis. Therefore, a comprehensive understanding of insulin and GH balance is essential for understanding endocrine hormonal contributions to energy storage and utilization. In this review we summarize the actions of, and interactions between, insulin and GH at the cellular level, and highlight the association between the insulin/GH ratio and energy metabolism, as well as fat accumulation. Use of the [insulin]:[GH] ratio as a biomarker for predicting the development of obesity is proposed.

Compared with central penetration, the eccentric penetration of jet into a liquid-filled composite armor (LCA) shows a more obvious lateral displacement due to the asymmetric impact by the shock wave and liquid radial reflux. Based on this characteristic, the reaming process in the liquid layer during the shaped charge jet (SCJ) penetrates into the strongly-constrained liquid-filled composite armor (SLCA) eccentrically, the interference process of jet is subjected to the asymmetric impact by the shock wave and liquid radial reflux, and the lateral movement process of the SCJ under lateral force loading is analyzed to study the influence of SLCA on the stability of incoming SCJ during eccentric penetration. Theoretical and X-ray experimental results show that when the eccentricity distance is [0 mm, 12 mm], the severely disturbed velocity range and total disturbed velocity range of the SCJ increase with the increase of the eccentricity distance, while the maximum lateral displacement of the SCJ decreases slightly with the increase of the eccentricity distance at [1 mm, 12 mm].

Fragmentation is the main energy dissipation form of foam concrete under explosion loading. To characterize the energy dissipation of foam concrete fragmentation quantitatively, explosion loading experiments of foam concrete plates under different stand-offs and plate thicknesses were carried out. The statistical characteristics of fragments and the energy dissipation law of foam concrete plate fragmentation were studied using image processing, fracture mechanics theory and fractal theory. An engineering calculation model of fragmentation fractal dimension and energy dissipation density of foam concrete plates were established. Results show that: the fragmentation of foam concrete plates under different explosion conditions is a fractal in the statistical sense. With the increase in stand-off and plate thickness, the fragment size of foam concrete plates increases, and the fragmentation fractal dimension decreases linearly. The linear relationship between the energy dissipation density and the fragmentation fractal dimension of foam concrete are expressed as D f = 0.0165 ω + 1.053.

The coating of polyurea elastomers on walls is a hotspot in the protection field. This work combines a numerical simulation with experimental validation to examine the blast resistance after coating a polyurea elastomer on a 370 mm wall under a contact explosion. Firstly, the failure limit, failure mode, and failure mechanism of the 370 mm unreinforced wall under different strength loads are studied. In the case of the contact explosion, the increase in size of the 370 mm wall blasting pit gradually stops after the dose is increased to more than 1 kg. Thereafter, the energy of the explosive load wis released by splashing wall fragments as well as by the deflection and movement of the wall. Spraying double-sided polyurea reinforcement on the wall can effectively improve the resistance to damages caused by exposure to explosive loads and can inhibit the damage to the surrounding personnel and equipment caused by flying structural debris. When the polyurea thickness on the front surface is 6 mm, the optimal thickness of the back surface should be 2 mm.

The process of liquid radial reflux interference during jet penetration in a liquid-filled composite structure is divided in this study into three stages: bottom plate reflection interference, side-wall reflection interference, and side-wall secondary reflection interference. The calculation model of the velocity interval of the disturbed jet and the residual penetration depth of the jet has been established through theoretical analysis. Results show that the liquid-filled composite structure can interfere with the high-speed section of the shaped charge jet. The accuracy of the theoretical analysis in this paper has been verified through numerical simulation, X-ray, and depth-of-penetration experiments. Among the results, those of the X-ray experiment show that the liquid-filled composite structure has interference on the tip of the shaped charge jet, which provides a possibility for the application of the liquid-filled composite structure to ammunition safety and other extreme cases.

Background: Insulin and growth hormone (GH) – 2 vital metabolic regulatory hormones – regulate glucose, lipid, and energy metabolism. These 2 hormones determine substrate and energy metabolism under different living conditions. Shift of day and night affects the clock system and metabolism probably through altered insulin and GH secretion. Methods: Five-week-old male mice were randomly assigned to a rotating light (RL) group (3-day normal light/dark cycle followed by 4-day reversed light/dark cycle per week) and normal light (NL) group. Body weight and food intake were recorded every week. Series of blood samples were collected for pulsatile GH analysis, glucose tolerance test, and insulin tolerance test at 9, 10, and 11 weeks from the start of intervention, respectively. Indirect calorimetric measurement was performed, and body composition was tested at 12 weeks. Expressions of energy and substrate metabolism-related genes were evaluated in pituitary and liver tissues at the end of 12-week intervention. Results: The RL group had an increased number of GH pulsatile bursts and reduced GH mass/burst. RL also disturbed the GH secretion regularity and mode. It suppressed insulin secretion, which led to a disturbed insulin/GH balance. It was accompanied by the reduced metabolic flexibility and modified gene expression involved in energy balance and substrate metabolism. Indirect calorimeter recording revealed that RL decreased the respiratory exchange ratio (RER) and oxygen consumption at the dark phase, which resulted in an increase in fat mass and free fatty acid levels in circulation. Conclusion: RL disturbed pulsatile GH secretion and decreased insulin secretion in male mice with significant impairment in energy, substrate metabolism, and body composition.

A type of high-voltage pulse source technology generating double-exponential waveform pulse group was introduced. In this approach, the pulse interval could be adjusted with the step length of 100 μs, and the amplitude would reach up to 35 kV. This pulse source could be used to test the sensitivity of electric vehicle (EV) piles under electrical fast transient (EFT) interference. The theory of obtaining double-exponential wave and its generating circuit was analyzed, and then the influencing factors of the rising edge were expounded. A method of pulse insertion was adopted to generate a fast transient pulse group due to the limitation of the repeated operating frequency of switching devices. This method could be summarized as a common load fed by several parallel pulse sources, which were controlled and triggered in time sequence. Thus, a set of timing pulse could be obtained from the load ending. The feasibility of this method was also demonstrated. The electromagnetic interference cannot be avoidable because the load was fed by different timing sources. The high-voltage pulse generated initially causes the latter sources to be false-triggered with serious influence to the entire system. The interference generated by the couple circuit composed by distributed parameters, such as distributed capacitance and inductance, was also analyzed. A coupled model was established, analyzed, and simulated to prove the existence of the conducted interference and false triggering for other sources. The measure of conducted interference suppression was also presented. A set of experiments was carried out to show that different numbers of double-exponential pulse groups with different time intervals could be obtained.

In order to study the influence mechanism of conical shock waves on pulsed laser forward detection, an analytical method is proposed for arbitrary Mach number and cone angle conditions. Based on traditional gas dynamics and physical optics, a simplified model of Gaussian beam transmission across the conical shock wave flow field is established. On this basis, combined with the process of pulsed laser detection, the analytical expression of pulsed laser echo waveform under the influence of shock wave is derived. Simulation results show that the conical shock wave under different conditions can lead to beam deflection, focus, and reflection to different degrees. Furthermore, the variation of echo waveform caused by aero-optical effect is also analyzed, and it is shown that the peak power, pulse width and arrival time of echo all fluctuate greatly with rolling motion at different shock angle and cone angle, among which the shift of the arrival time and the reflection effect of shock wave have the largest impact on laser detection.

How to effectively reduce the damage of frequent accidental explosions and explosion attacks to existing walls is an important concern of the blast resistance field. In the present study, the influence of the foamed concrete (density 820 kg/m3, water-cement ratio 0.4) coating thickness on the blast resistance of a 120 mm RC (reinforced concrete) wall was studied through blast experiments, numerical simulations, and shock wave theory. Results show that the influences of foamed concrete on the blast resistance of RC walls are jointly decided by the stress drop caused by impedance effect and exponential attenuation and the stress rise caused by high-speed impact compression. The coating thickness mainly affects the foam concrete’s fragmentation degree and stress attenuation. A lower critical coating thickness exists in foamed concrete-coated RC walls. The blast resistance of the RC wall will decrease when the coating thickness is less than that value. The lower critical coating thickness is related to the intensity of blast load and the energy absorption capacity of foamed concrete, and it can be predicted by monitoring the explosive stress and energy incident to the RC wall.

Clinical studies have reported that miRNAs abnormal expression are associated with the generation of cisplatin-resistant to osteosarcoma. Our previous research found that miR-203 is downregulated in osteosarcoma cells and overexpressed miR-203 exerts antitumor properties on osteosarcoma cells. However, the role and mechanism of miR-203 in regulating the sensitivity of cisplatin in osteosarcoma cells remains unclear. This study aimed to investigate the effects of miR-203 in cisplatin therapy for osteosarcoma cells

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH-releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered their clinical application. Here, we tested whether stimulation of endogenous GH secretion by a synthetic GH secretagogue receptor (GHSR) agonist, hexarelin, improved the metabolism in a hyperphagic obese mouse model. Male melanocortin 4 receptor knockout mice (MC4RKO) were pair-fed and received continuous hexarelin (10.56 μg/day) or vehicle infusion by an osmotic pump for 3-4 weeks. Hexarelin treatment significantly increased the pulsatile GH secretion without detectable alteration on basal GH secretion in MC4RKO mice. The treated mice showed increased lipolysis and lipid oxidation in the adipose tissue, and reduced de novo lipogenesis in the liver, leading to reduced visceral fat mass, reduced triglyceride content in liver, and unchanged circulating free fatty acid levels. Importantly, hexarelin treatment improved the whole-body insulin sensitivity but did not alter glucose tolerance, insulin levels, or insulin-like growth factor 1 (IGF-1) levels. The metabolic effects of hexarelin were likely through the direct action of GH, as indicated by the increased expression level of genes involved in GH signaling pathways in visceral adipose tissues and liver. In conclusion, hexarelin treatment stimulated the pulsatile GH secretion and reduced the fat accumulation in visceral depots and liver in obese MC4RKO mice with improved insulin sensitivity without altered levels of insulin or IGF-1. It provides evidence for managing obesity by enhancing pulsatile GH secretion through activation of GHSR in the pituitary gland.

Objective: This proof-of-concept study aimed to evaluate the efficacy and safety of suppression of insulin secretion in the treatment of obesity. Methods: A search of PubMed, Embase, and Cochrane databases was performed to identify randomized controlled trials (up to January 1, 2020) that used drugs that directly suppress insulin secretion (diazoxide or octreotide) in the treatment of obesity. The extracted data were analyzed using random-effects meta-analysis. Results: A total of seven randomized controlled trials were included, with four using diazoxide and three using octreotide to suppress insulin secretion. Suppression of insulin secretion significantly reduced fasting insulin level (mean difference: −3.94 mIU/L; 95% CI: −7.40 to −0.47) but slightly increased fasting blood glucose level (mean difference: 0.48 mmol/L; 95% CI: 0.24 to 0.72). Following the suppression of insulin secretion, significant reductions in body weight (mean difference: −3.19 kg; 95% CI: −5.71 to −0.66), BMI (mean difference: −1.65 kg/m2; 95% CI: −2.41 to −0.90), and fat mass (mean difference: −5.92 kg; 95% CI: −8.28 to −3.56) were observed compared with placebo in the pooled data. No significant difference in fat-free mass was observed (mean difference: 0.56 kg; 95% CI: −0.40 to 1.52). Conclusions: Results suggest that suppression of insulin secretion may lead to reduced body weight and fat mass with slightly increased blood glucose in individuals with obesity.

Insulin and growth hormone (GH) are crucial counter-regulatory hormones in regulating glucose and lipid metabolisms. Insulin promotes fat storage, while GH promotes lipolysis and fat oxidation. In obese individuals, reduced GH secretion (hyposomatotropism) and increased insulin secretion (hyperinsulinemia) co-exist. The imbalance of these two hormones exacerbates fat accumulation. Therapeutic approaches to correct such hormonal imbalance in obesity are limited. The sodium/glucose cotransporter 2 inhibitor (SGLT2i), which promotes urinary glucose excretion, is a novel drug for overt type 2 diabetes (T2D). However, little is known about its efficacy in obese individuals without T2D in the clinic, in particular with hormonal imbalance. By applying SGLT2i (dapagliflozin, 1 mg/kg/d for 10 weeks) to a hyperphagic obese melanocortin 4 receptor knockout (MC4RKO) mouse model, we observed a significant reduction of hyperinsulinemia (fasting: 1.36±0.19 vs. 4.93±1.04 ng/ml, p Acknowledgements: grant (NHMRC, University of Queensland) and scholarship (CSC and UQ International scholarship) Reference: (1) Huang, Zhengxiang, et al. “Dapagliflozin restores insulin and growth hormone secretion in obese mice.” Journal of Endocrinology 245.1 (2020): 1-12. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Like many other neuroendocrine hormones, growth hormone (GH; somatotropin) secretion is pulsatile with regular releasing bursts on a relatively low constitutive basal secretion. This chapter discusses current knowledge of the regulation and the function of GH pulsatile profiles, with new development of laboratory approaches and introduces knowledge about GH functions on metabolic regulation in addition to the conventional concept of a role in regulating body growth. As reported in the literature, amplitude, frequency, and regularity of GH secretion are tightly linked to metabolic conditions with clear species and gender differences. In response to negative and positive energy balances, the GH pulsatile pattern changes to mobilize or store energy in adipose, muscle, and liver in order to accommodate the changing nutritional conditions. Changes in GH pulsatility are achieved through regulating the hypothalamo–pituitary GH axis with altered levels of key stimulatory and inhibitory hormones, GH-releasing hormone (GHRH) and somatostatin (SRIF, somatotropin release inhibiting factor). The hypothalamic–pituitary GH axis is constantly under the influence of peripheral metabolic factors, such as lipid and glucose levels; peripheral metabolic regulatory hormones, such as leptin and insulin; and central metabolic regulatory neuropeptides, such as neuropeptide Y and melanocortin. Regulation of the hypothalamic–pituitary GH axis is achieved through activation of cell membrane receptors, intracellular signaling pathways, and membrane ion channels. Detailed regulatory mechanisms are discussed in this chapter in order to understand the coupling of cell electrophysiological properties and the hormone secretory process of exocytosis in hypothalamic neurons and pituitary GH-secreting somatotrophs. Technical advances in electrophysiology, cell imaging analysis, and real-time in vivo hormone analysis are discussed to deepen the understanding of physiological and pathophysiological regulation of GH secretion. Future directions are also discussed, as are unanswered questions in this field.

Chemoresistance implicates the therapeutic value of cisplatin and remains a primary obstacle to its clinical use. MicroRNAs (miRs) negatively modulate the expression of their target genes and are associated with the occurrence and progression of various types of tumor. The abnormal expression of miR-504 has been reported in certain types of human tumor and has been associated with tumor prognosis. However, the association between miR-504 and cisplatin in human osteosarcoma remains unclear. The present study therefore aimed to assess the in vitro effects and possible mechanism of miR-504 in cell proliferation, apoptosis and cisplatin resistance in MG63 osteosarcoma cells. The results demonstrated that miR-504 was overexpressed in osteosarcoma tissues and cells. This overexpression also induced cell proliferation, as determined by MTT and EdU staining assays. Furthermore, miR-504 suppressed cisplatin-induced apoptosis, which was demonstrated via MTT, cell morphology analysis and flow cytometry. Cisplatin-induced G1 arrest was also suppressed, which was determined by flow cytometry. The potential target genes of miR-504 were predicted using bioinformatics. p53 was confirmed to be a direct target of miR-504 using a luciferase reporter assay and western blot analysis revealed that miR-504 negatively regulated p53 expression at a molecular level. These results indicate that miR-504 contributes to cisplatin resistance in MG63 osteosarcoma cells by suppressing p53. miR-504 may therefore be a potential biomarker for cisplatin resistance in patients with osteosarcoma.

Glucosamine is effective in the treatment of osteoarthritis; however, its effect on osteoporosis remains unclear. Decreased activity of osteoblasts is the main cause of osteoporosis. Here, we examined the effects of glucosamine on osteoblasts. The potential underlying mechanisms were explored. The results showed that glucosamine had a biphasic effect on the viability of hFOB1.19 osteoblasts. At low concentrations (0.6 mM), glucosamine induced hFOB1.19 cell proliferation, whereas at high concentrations (0.8 mM) it induced apoptosis. The autophagy inhibitor 3-methyladenine (3-MA) was used to verify that glucosamine modulated hFOB1.19 cell viability via autophagy. The induction of apoptosis by high concentrations of glucosamine was significantly exacerbated by 3-MA, whereas the promotion of cell proliferation by low concentrations of glucosamine was significantly suppressed by 3-MA. Autophagy was examined by western blot detection of autophagy-related proteins including LC3, Beclin-1, and SQSTM1/p62 and by immunofluorescence analysis of autophagosomes. Glucosamine activated autophagy in a time- and concentration-dependent manner. Investigation of the underlying mechanism showed that glucosamine inhibited the phosphorylation of m-TOR in a concentration-dependent manner within 48 h, and rapamycin significantly inhibited the phosphorylation of m-TOR. These results demonstrated that glucosamine promoted hFOB1.19 cell proliferation and increased autophagy by inhibiting the m-TOR pathway, suggesting its potential as a therapeutic agent for osteoporosis.

MicroRNA-21 (miR-21) contributes to anti-apoptosis in bone marrow mesenchymal stem cells (BMSC), but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible effect of miR-21 on regulating BMSCs directional migration and the expression of MMP-2/MMP-9 in BMSCs in vitro. BMSCs were successfully infected with miR-21-up lentivirus. Cell migration using Transwell assay indicated that upregulated expression of miR-21 could significantly promote BMSCs migration. Western blot analysis indicated that miR-21 significantly upregulated the expression of MMP-2 and MMP-9, which were related to metastasis-associated genes. GM6001, the specific MMPs inhibitor, abrogated the upregulated expression of MMP-2/MMP-9 and abolished the positive effect of miR-21 on promoting BMSCs migration. Meanwhile, miR-21 significantly enhanced Akt phosphorylation, as measured by Western blot analysis. LY294002, an inhibitor of Akt activation, abrogated the phosphorylation of Akt and abolished the positive effect of miR-21 on promoting BMSCs migration and upregulating MMP-2/MMP-9 expression. These results suggest that miR-21 contributes to BMSCs migration by upregulating MMP-2/MMP-9, potentially via the PI3K/Akt pathway.

Accumulating evidence indicates that microRNA-203 (miR-203) is abnormally expressed in many human tumor tissues and significantly associated with the occurrence, development and clinical outcomes of human tumors. The aim of this study was to determine the target genes and functional significance of miR-203 in osteosarcoma cells. We found reduced expression of miR-203 in osteosarcoma tissues and cells (MG63 and U2-OS) compared with the adjacent normal tissues and normal osteoblastic cells (hFOB1.19), respectively. In vitro studies further demonstrated that exogenous miR-203 overexpression inhibited osteosarcoma cell proliferation and invasion, and promoted apoptosis. At the molecular level, our results confirmed that apoptosis, cell cycle and invasion-related proteins were regulated by miR-203. Our findings also revealed that Runt-related transcription factor 2 (RUNX2) was directly negatively regulated by miR-203. These results suggested that miR-203 may function as a tumor suppressor and may therefore have therapeutic potential in the treatment of human osteosarcoma.