Publications by authors named "Zhengxiang Huang"

18 Publications

  • Page 1 of 1

Suppression of hyperinsulinemia restores growth hormone secretion and metabolism in obese mice.

J Endocrinol 2021 Jul 12;250(3):105-116. Epub 2021 Jul 12.

School of Biomedical Sciences, University of Queensland, Queensland, Australia.

The well-balanced secretion between insulin and growth hormone (GH) is essential in regulating substrate metabolism, energy metabolism, and body composition. High insulin and low GH levels are often observed in obesity, contributing to reduced energy expenditure and further fat accumulation. Although suppression of hyperinsulinemia is proposed as a treatment for obesity, changes in GH secretion and energy metabolism following this treatment are not thoroughly studied. This leaves unexplained observations, such as unchanged lean mass following insulin reduction. In this study, high-fat diet-induced obese (DIO) and normal chow-fed lean mice on a C57BL/6J background were treated for 7 weeks with diazoxide (1250 mg/kg in food), a KATP channel opener that suppressed insulin secretion. Diazoxide treatment for 10 days was sufficient to increase pulsatile GH secretion in DIO mice before any significant body weight change. The restored insulin-GH balance in DIO mice was followed by improvement in substrate and energy metabolism in a prolonged treatment period (4-6 weeks), including reduced fat mass, increased lipid oxidation and energy expenditure, as well as improved insulin sensitivity and metabolic flexibility. These metabolic benefits occurred along with the changes in the expression level of genes regulated by the insulin-GH balance. When applying diazoxide to normal chow-fed normoinsulinemic lean mice, none of the above metabolic effects was observed, suggesting that the metabolic changes following diazoxide treatment were mediated through the suppression of hyperinsulinemia. These results suggest that suppression of hyperinsulinemia by diazoxide restores GH secretion and improves substrate and energy metabolism in DIO mice.
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http://dx.doi.org/10.1530/JOE-20-0616DOI Listing
July 2021

Knockdown of microRNA-203 reduces cisplatin chemo-sensitivity to osteosarcoma cell lines MG63 and U2OS by targeting RUNX2.

J Chemother 2021 Mar 25:1-14. Epub 2021 Mar 25.

Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

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 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 by targeting RUNX2, and speculated that miR-203 may be a target for drug resistance of osteosarcoma to cisplatin.
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http://dx.doi.org/10.1080/1120009X.2021.1899441DOI Listing
March 2021

Time-restricted feeding restored insulin-growth hormone balance and improved substrate and energy metabolism in MC4RKO obese mice.

Neuroendocrinology 2021 Mar 18. Epub 2021 Mar 18.

Background Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone Insulin-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 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 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 expression 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.
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http://dx.doi.org/10.1159/000515960DOI Listing
March 2021

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice.

FASEB J 2021 01;35(1):e21269

School of Biomedical Sciences, University of Queensland, St Lucia, QLD, Australia.

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.
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http://dx.doi.org/10.1096/fj.202001924RRDOI Listing
January 2021

Suppression of Insulin Secretion in the Treatment of Obesity: A Systematic Review and Meta-Analysis.

Obesity (Silver Spring) 2020 11;28(11):2098-2106

School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Queensland, Australia.

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/m ; 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.
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http://dx.doi.org/10.1002/oby.22955DOI Listing
November 2020

Insulin and Growth Hormone Balance: Implications for Obesity.

Trends Endocrinol Metab 2020 09 13;31(9):642-654. Epub 2020 May 13.

School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Australia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.tem.2020.04.005DOI Listing
September 2020

Piperlongumine induces apoptosis and G/M phase arrest in human osteosarcoma cells by regulating ROS/PI3K/Akt pathway.

Toxicol In Vitro 2020 Jun 24;65:104775. Epub 2020 Jan 24.

Department of Orthopedics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. Electronic address:

Previous research has reported that piperlongumine exerts antitumor properties on several types of tumor cells. However, its effect on osteosarcoma cells remains unknown. This study aimed to investigate the antitumor effects of piperlongumine on osteosarcoma cells (MG63 and U2OS cells) in vitro and determined the underlying mechanism. Cell viability was measured using MTT assay. Cell apoptosis was assessed via AO/EB staining and flow cytometry apoptosis as well as western blot analysis. Cell cycle distribution was detected by flow cytometric cell cycle and western blot analysis. In our research, we found that piperlongumine induced apoptosis and G/M phase arrest of MG63 cells. Western blot analysis not only confirmed the above results, but also demonstrated that piperlongumine induced apoptosis of osteosarcoma cells by activating Caspase-9-dependent apoptotic pathway. Furthermore, we also found that piperlongumine significantly induced apoptosis and cell cycle arrest of osteosarcoma cells by regulating ROS/PI3K/Akt signaling pathway. In summary, our findings suggested that piperlongumine inhibited osteosarcoma progression by promoting apoptosis of osteosarcoma cells. In addition, the underlying mechanism demonstrated that piperlongumine produced potent antitumor properties in osteosarcoma cells by regulating ROS/PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1016/j.tiv.2020.104775DOI Listing
June 2020

Dapagliflozin restores insulin and growth hormone secretion in obese mice.

J Endocrinol 2020 04;245(1):1-12

School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Australia.

The well-documented hormonal disturbance in a general obese population is characterised by an increase in insulin secretion and a decrease in growth hormone (GH) secretion. Such hormonal disturbance promotes an increase in fat mass, which deteriorates obesity and accelerates the development of insulin resistance and type 2 diabetes. While the pathological consequence is alarming, the pharmaceutical approach attempting to correct such hormonal disturbance remains limited. By applying an emerging anti-diabetic drug, the sodium-glucose cotransporter 2 inhibitor, dapagliflozin (1 mg/kg/day for 10 weeks), to a hyperphagic obese mouse model, we observed a significant improvement in insulin and GH secretion as early as 4 weeks after the initiation of the treatment. Restoration of pathological disturbance of insulin and GH secretion reduced fat accumulation and preserved lean body mass in the obese animal model. Such phenotypic improvement followed with concurrent improvements in glucose and lipid metabolism, insulin sensitivity, as well as the expression of metabolic genes that were regulated by insulin and GH. In conclusion, 10 weeks of treatment with dapagliflozin effectively reduces hyperinsulinemia and restores pulsatile GH secretion in the hyperphagic obese mice with considerable improvement in lipid and glucose metabolism. Promising outcomes from this study may provide insights into drug intervention to correct hormonal disturbance in obesity to delay the diabetes progression.
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http://dx.doi.org/10.1530/JOE-19-0385DOI Listing
April 2020

Rhythmic growth hormone secretion in physiological and pathological conditions: Lessons from rodent studies.

Mol Cell Endocrinol 2019 12 6;498:110575. Epub 2019 Sep 6.

School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Australia. Electronic address:

Evolutionally conserved in all mammalians, the release of GH occurs in a rhythmic pattern, characterized by several dominant surges (pulsatile GH) with tonic low inter-pulse levels (tonic GH). Such pulsatile secretion pattern is essential for many physiological actions of GH on different tissues with defined gender dimorphism. Rhythmic release of pulsatile GH is tightly controlled by hypothalamic neurons as well as peripheral metabolic factors. Changes of GH pattern occur within a range of sophisticated physiological and pathological settings and significantly contribute to growth, ageing, survival and disease predispositions. Precise analysis of GH secretion pattern is vitally important for a comprehensive understanding of the function of GH and the components that regulate GH secretion pattern.
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http://dx.doi.org/10.1016/j.mce.2019.110575DOI Listing
December 2019

Effects of Liquid Parameters on Liquid-Filled Compartment Structure Defense Against Metal Jet.

Materials (Basel) 2019 Jun 4;12(11). Epub 2019 Jun 4.

Department of Mechanics and Engineering Science, Nanjing University of Science and Technology, Nanjing 210094, China.

The effect of liquid parameters on the defense capability of the liquid-filled compartment structure (LFCS) of a shaped charge jet (SCJ) is quantified using dimension analysis of experiments on the reduced depth of SCJ penetration, which is disturbed via the LFCS with different liquids. The effects of three parameters, namely, liquid density, sound velocity and dynamic viscosity, on LFCS defense for SCJ are discussed quantitatively. Dynamic viscosity exerts the most important effect on LFCS disturbance of SCJ penetration, followed by liquid density. Meanwhile, sound velocity causes a negligible effect on LFCS disturbance of SCJ when the hole diameter in LFCSs are short. LFCSs offer excellent protection as they can significantly reduce the penetration capability of SCJ. Thus, LFCSs can be used as a new kind of armor for defense against SCJ.
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http://dx.doi.org/10.3390/ma12111809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600728PMC
June 2019

Salidroside suppresses the growth and invasion of human osteosarcoma cell lines MG63 and U2OS in vitro by inhibiting the JAK2/STAT3 signaling pathway.

Int J Oncol 2019 Jun 10;54(6):1969-1980. Epub 2019 Apr 10.

Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Previous research has reported that salidroside exerts antitumor properties on numerous types of tumor cells; however, its effect on osteosarcoma cells remains unknown. The present study aimed to investigate the effects of salidroside on the viability, apoptosis and invasion of osteosarcoma cells in vitro, and determine the underlying mechanism of action. The results of an MTT revealed that salidroside suppressed the viability of osteosarcoma cells (MG63 and U2OS cells) in a time‑ and concentration‑dependent manner. The results of cell morphological analysis (profile observations and Hoechst 33258 staining) and the detection of apoptosis by flow cytometry further indicated that the decrease in osteosarcoma cell viability induced by salidroside was associated with cell apoptosis. Western blot analysis not only confirmed these results but also suggested that salidroside induced the apoptosis of osteosarcoma cells by activating the caspase‑9‑dependent apoptotic pathway. In addition, we reported that salidroside induced G0/G1 phase arrest and suppressed the invasion of osteosarcoma cells, as measured by flow cytometric cell cycle analysis and a Transwell invasion assay, respectively. Western blot analysis confirmed the aforementioned results. Furthermore, our findings demonstrated that salidroside induced the apoptosis, G0/G1 phase arrest and suppressed the invasion of osteosarcoma cells by inhibiting the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, as determined by western blot analysis. In summary, the findings of the present study suggested that salidroside may inhibit the progression of osteosarcoma by suppressing the growth and invasion of osteosarcoma cells. Furthermore, the investigations into the underlying mechanism demonstrated that salidroside exerted notable antitumor activity in osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway.
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http://dx.doi.org/10.3892/ijo.2019.4781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521935PMC
June 2019

MicroRNA-504 modulates osteosarcoma cell chemoresistance to cisplatin by targeting p53.

Oncol Lett 2019 Feb 22;17(2):1664-1674. Epub 2018 Nov 22.

Department of Orthopaedics and Traumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.

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 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 G 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.
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http://dx.doi.org/10.3892/ol.2018.9749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341607PMC
February 2019

Glucosamine promotes osteoblast proliferation by modulating autophagy via the mammalian target of rapamycin pathway.

Biomed Pharmacother 2018 Mar;99:271-277

Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biopha.2018.01.066DOI Listing
March 2018

MicroRNA-21 promotes bone mesenchymal stem cells migration in vitro by activating PI3K/Akt/MMPs pathway.

J Clin Neurosci 2017 Dec 26;46:156-162. Epub 2017 Aug 26.

Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jocn.2017.07.040DOI Listing
December 2017

Downregulation of calbindin 1, a calcium-binding protein, reduces the proliferation of osteosarcoma cells.

Oncol Lett 2017 May 28;13(5):3727-3733. Epub 2017 Mar 28.

Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.

Osteosarcoma is the most common type of primary malignant bone tumor and has a high propensity to metastasize to the lungs and bones. Calbindin 1 () is a constituent Ca2+ binding protein, which can prevent apoptotic death in several cell types induced through various pro-apoptotic signaling pathways. To investigate whether is implicated in the tumor growth of human osteosarcoma, two different short hairpin RNAs (shRNAs) against were used for -knockdown in osteosarcoma U2OS cells. The U2OS cells were divided into three groups: Two groups with knockdown (CALB1-shRNA 1 and CALB1-shRNA 2) and one control group (Con-shRNA). Reverse transcription-quantitative polymerase chain reaction and western blot analysis confirmed that the CALB1-shRNA 1- and 2-infected cells exhibited significantly lower levels of gene and protein expression compared with the Con-shRNA group. The proliferation and colony formation abilities were significantly inhibited in -deficient U2OS cells compared with the control, as measured using an MTT assay and crystal violet staining. Flow cytometry revealed that the number of CALB1-shRNA 2-injected cells was increased in the G/G and G/M phases, but decreased in the S phase, compared with the control group. The assessment of apoptosis and necrosis using Annexin V/7-aminoactinomycin D demonstrated that there was a significantly higher percentage of necrotic, early apoptotic, and late apoptotic cells, but a significantly lower percentage of viable cells in U2OS cells with -knockdown compared with the control group. In conclusion, contributes to protecting osteosarcoma cells from apoptosis and provides a potential novel target for gene therapy to treat patients with osteosarcoma.
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http://dx.doi.org/10.3892/ol.2017.5931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431599PMC
May 2017

MicroRNA-203 inhibits proliferation and invasion, and promotes apoptosis of osteosarcoma cells by targeting Runt-related transcription factor 2.

Biomed Pharmacother 2017 Jul 15;91:1075-1084. Epub 2017 May 15.

Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.biopha.2017.05.034DOI Listing
July 2017

Associations of polymorphisms in NAT2 gene with risk and metastasis of osteosarcoma in young Chinese population.

Onco Targets Ther 2015 22;8:2675-80. Epub 2015 Sep 22.

Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Osteosarcoma is the most common primary malignancy of bone in young individuals. Genetic factors may play an important role in the tumorigenesis of osteosarcoma. Here we carried out a case-control study to investigate seven NAT2 single-nucleotide polymorphisms (rs1799929, rs120, rs1041983, rs1801280, rs1799930, rs1799931, and rs1801279) on the risk and prognosis of osteosarcoma. This study included 260 young osteosarcoma cases and 286 controls. The TaqMan method was used to determine genotypes. We found that rs1799931 G>A polymorphisms were associated with a decreased risk of osteosarcoma in young Chinese population, and rs1041983 CT genotype seemed to play a protective role in the risk of osteosarcoma. However, further analysis showed that rs1041983 polymorphisms were associated with an elevated risk of tumor metastasis, predicting poor prognosis. This study provided the first evidence for the associations between NAT2 polymorphisms and osteosarcoma risk and metastasis in Chinese population.
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http://dx.doi.org/10.2147/OTT.S92275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590633PMC
October 2015

Berberine improves endothelial function by inhibiting endoplasmic reticulum stress in the carotid arteries of spontaneously hypertensive rats.

Biochem Biophys Res Commun 2015 Mar 14;458(4):796-801. Epub 2015 Feb 14.

Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China. Electronic address:

Activation of endoplasmic reticulum (ER) stress in endothelial cells leads to increased oxidative stress and often results in cell death, which has been implicated in hypertension. The present study investigated the effects of berberine, a botanical alkaloid purified from Coptidis rhizoma, on ER stress in spontaneously hypertensive rats (SHRs) and the underling mechanism. Isolated carotid arteries from normotensive WKYs and SHRs were suspended in myograph for isometric force measurement. Protein phosphorylations and expressions were determined by Western blotting. Reactive oxygen species (ROS) level was measured by DHE staining. SHR carotid arteries exhibited exaggerated acetylcholine-triggered endothelium-dependent contractions (EDCs) and elevated ROS accumulation compared with WKY arteries. Moreover, Western blot analysis revealed the reduced AMPK phosphorylation, increased eIF2α phosphorylation, and elevated levels of ATF3, ATF6, XBP1 and COX-2 in SHR carotid arteries while these pathological alterations were reversed by 12 h-incubation with berberine. Furthermore, AMPK inhibitor compound C or dominant negative AMPK adenovirus inhibited the effects of berberine on above-mentioned marker proteins and EDCs. More importantly, ROS scavengers, tempol and tiron plus DETCA, or ER stress inhibitors, 4-PBA and TUCDA normalized the elevated levels of ROS and COX-2 expression, and attenuated EDCs in SHR arteries. Taken together, the present results suggest that berberine reduces EDCs likely through activating AMPK, thus inhibiting ER stress and subsequently scavenging ROS leading to COX-2 down-regulation in SHR carotid arteries. The present study thus provides additional insights into the vascular beneficial effects of berberine in hypertension.
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http://dx.doi.org/10.1016/j.bbrc.2015.02.028DOI Listing
March 2015