Mir-Oz Kegulates Osteoblast Apoptosis, Proliferation and Differentiation through Targeted Inhibition of Runx2 in Osteoporosis Running Title: Role and Potential Mechanism of Mir-152 in Osteoporosis

2021 ◽  
Vol 7 (5) ◽  
pp. 4005-4012
Author(s):  
Peng Shi ◽  
Yujie Sun ◽  
Jing Huang ◽  
Lugang Zhou
Keyword(s):  
Cell Proliferation ◽  
Biological Indicator ◽  
Biological Behavior ◽  
Potential Mechanism ◽  
Serum Samples ◽  
Differentiation Markers ◽  
Osteoblast Cell Line ◽  
Auc Value ◽  
Targeted Inhibition ◽  
In Cells

Objective: To explore the role and potential mechanism of miR-152 in osteoporosis. Methods: Fifty-four osteoporotic patients and 54 healthy subjects were recruited from August 2017 to January 2019. Serum samples of the two groups were obtained, and the miR-152 expression in serum was detected and compared. The human osteoblast cell line hFOB1.19 was obtained and miR-152 in cells was increased. The biological behavior changes such as cell proliferation, apoptosis and differentiation were observed by MTT, flow cytometry and detection of osteoblast differentiation markers (ALP, OCN). Results: miR-152 was elevated in osteoporosis patients, and AUC value of serum miR-152 in diagnosing osteoporosis was 0.939. After miR-152 in osteoblasts was elevated, cell proliferation was inhibited, cell apoptosis rate increased, and ALP and OCN content in cells reduced, while increasing cell RUNX2 simultaneously was totally different. Dual luciferase report showed that RUNX2 could be targeted and regulated by miR-152. Conclusion: miR-152 is elevated in serum of osteoporosis patients and can be used as a biological indicator for diagnosing osteoporosis. In addition, miR-152 can inhibit osteoblast proliferation, differentiation and induce apoptosis through negative regulation of RUNX2.

scholarly journals Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1376
Author(s):  
Concettina Cappadone ◽  
Emil Malucelli ◽  
Maddalena Zini ◽  
Giovanna Farruggia ◽  
Giovanna Picone ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Magnesium Deficiency ◽  
Acid Synthesis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
High Concentration ◽  
Proliferating Cells ◽  
Intracellular Magnesium ◽  
In Cells

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2–3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

scholarly journals Polyamine Biosynthetic Pathway as a Drug Target for Osteosarcoma Therapy

2018 ◽  
Vol 6 (3) ◽  
pp. 65 ◽  
Author(s):  
Rebecca Weicht ◽  
Chad Schultz ◽  
Dirk Geerts ◽  
Katie Uhl ◽  
André Bachmann
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Cell Lines ◽  
High Performance ◽  
Tumor Development ◽  
Oral Drug ◽  
Differentiation Markers ◽  
Cellular Effects ◽  
Medical Advances

Osteosarcoma (OS) is the most common bone tumor in children. Polyamines (PAs) are ubiquitous cations involved in many cell processes including tumor development, invasion and metastasis. In other pediatric cancer models, inhibition of the PA biosynthesis pathway with ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) results in decreased cell proliferation and differentiation. In OS, the PA pathway has not been evaluated. DFMO is an attractive, orally administered drug, is well tolerated, can be given for prolonged periods, and is already used in pediatric patients. Three OS cell lines were used to study the cellular effects of PA inhibition with DFMO: MG-63, U-2 OS and Saos-2. Effects on proliferation were analyzed by cell count, flow cytometry-based cell cycle analysis and RealTime-Glo™ MT Cell Viability assays. Intracellular PA levels were measured with high-performance liquid chromatography (HPLC). Western blot analysis was used to evaluate cell differentiation. DFMO exposure resulted in significantly decreased cell proliferation in all cell lines. After treatment, intracellular spermidine levels were drastically decreased. Cell cycle arrest at G2/M was observed in U-2 OS and Saos-2. Cell differentiation was most prominent in MG-63 and U-2 OS as determined by increases in the terminal differentiation markers osteopontin and collagen 1a1. Cell proliferation continued to be suppressed for several days after removal of DFMO. Based on our findings, DFMO is a promising new adjunct to current osteosarcoma therapy in patients at high risk of relapse, such as those with poor necrosis at resection or those with metastatic or recurrent osteosarcoma. It is a well-tolerated oral drug that is currently in phase II clinical trials in pediatric neuroblastoma patients as a maintenance therapy. The same type of regimen may also improve outcomes in osteosarcoma patients in whom there have been essentially no medical advances in the last 30 years.

Steroid-induced cell proliferation in vivo is associated with increased c-myc proto-oncogene transcript abundance

Development ◽  
1988 ◽  
Vol 104 (1) ◽  
pp. 87-95
Author(s):  
S.A. Rempel ◽  
R.N. Johnston
Keyword(s):  
Cell Proliferation ◽  
Growth Factors ◽  
Steroid Hormones ◽  
Steroid Hormone ◽  
Normal Liver ◽  
Transcript Abundance ◽  
Chicken Oviduct ◽  
Massive Cell ◽  
In Cells

Enhanced c-myc transcript abundance has been observed in a variety of human malignancies, in normal liver tissue induced to proliferate in vivo by partial hepatectomy and in cells in culture induced to proliferate with the addition of protein hormones and growth factors. Little is known, however, about the expression of cellular proto-oncogenes in cells induced to proliferate in vivo by steroid hormones. Experiments reported here indicate that when cells of the immature chicken oviduct are induced to undergo rapid in vivo proliferation by application of the estrogen hormone 17 beta-estradiol, the onset of this proliferation is associated with a rapid, large, and transient increase in c-myc transcript abundance. When estrogen is administered to chickens in which the oviduct has already differentiated, neither massive cell proliferation nor large increases in c-myc transcript abundance are induced. We conclude that the abundance of c-myc transcripts in vivo correlates well with the degree of cell proliferation induced by steroid hormone.

Chordoma of the skull base: predictors of tumor recurrence

2003 ◽  
Vol 98 (4) ◽  
pp. 812-822 ◽  
Author(s):  
Roberto Pallini ◽  
Giulio Maira ◽  
Francesco Pierconti ◽  
Maria Laura Falchetti ◽  
Ester Alvino ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Microsatellite Instability ◽  
Skull Base ◽  
Tumor Recurrence ◽  
Doubling Time ◽  
P53 Protein ◽  
Biological Behavior ◽  
Htert Mrna ◽  
Content Type ◽  
Fine Print

Object. Chordomas of the skull base are generally regarded as slow-growing tumors; however, approximately 20% of these lesions have been shown to recur as early as 1 year postsurgery. The classic pathological paradigms are poor predictors of outcome, and additional markers are needed to identify patients at risk for early tumor recurrence. In this study the authors describe such a marker. Methods. In a series of 26 patients with chordomas of the skull base, the authors investigated the relationship between the biological behavior of the tumor, which was determined according to the interval for its recurrence and volume doubling time, and several pathological and molecular features, which included the histological variant, proliferative activity, mutation of p53 protein, expression of human telomerase reverse transcriptase (hTERT) messenger (m)RNA, loss of heterozygosity (LOH), and microsatellite instability. The major finding in this study was that hTERT mRNA expression in chordoma cells identifies those tumors that exhibit unusually fast rates of growth. The expression of hTERT mRNA was frequently associated with mutation of p53 protein, indicating that telomerase dysfunction combines with abnormal p53 function to initiate the unrestrained clonal expansion of the tumor cells. In cases in which the tumor was partially removed, mutation of p53 protein and expression of hTERT mRNA predicted increased doubling time for residual tumor as well as the probability of tumor recurrence. Cell proliferation, as investigated using the Ki-67 method, was significantly related to the tumor doubling time; however, the authors found that the pattern of cell proliferation was not homogeneous throughout the chordoma tissue, and that the proliferative index might change by a factor as high as 8 among different regions of the same tumor. The LOH and microsatellite instability do not seem to affect the prognosis of skull base chordomas. Conclusions. Reactivation of telomerase in chordomas is a reliable predictor of outcome. The ability to predict the biological behavior of chordomas might have immediate implications in the management of this disease in patients who undergo surgery.

The Role of Nitric Oxide on the Proliferation of a Human Osteoblast Cell Line Stimulated With Hydroxyapatite

2008 ◽  
Vol 34 (4) ◽  
pp. 196-202 ◽  
Author(s):  
Wihaskoro Sosroseno ◽  
Erwan Sugiatno ◽  
Abdul Rani Samsudin ◽  
Mohd Fikri Ibrahim
Keyword(s):  
Nitric Oxide ◽  
Cell Proliferation ◽  
Cell Line ◽  
No Production ◽  
Human Osteoblast ◽  
Osteoblast Cell ◽  
Human Osteoblast Cell ◽  
Integrin Αv ◽  
Osteoblast Cell Line ◽  
Nitrite Production

Abstract The aim of the present study was to test the hypothesis that the proliferation of a human osteoblast cell line (HOS cells) stimulated with hydroxyapatite (HA) may be regulated by nitric oxide (NO). The cells were cultured on the surface of HA. Medium or cells alone were used as controls. L-arginine, D-arginine, 7-NI (an nNOS inhibitor), L-NIL (an iNOS inhibitor), L-NIO (an eNOS inhibitor) or carboxy PTIO, a NO scavenger, was added in the HA-exposed cell cultures. The cells were also precoated with anti-human integrin αV antibody. The levels of nitrite were determined spectrophotometrically. Cell proliferation was assessed by colorimetric assay. The results showed increased nitrite production and cell proliferation by HA-stimulated HOS cells up to day 3 of cultures. Anti-integrin αV antibody, L-NIO, or carboxy PTIO suppressed, but L-arginine enhanced, nitrite production and cell proliferation of HA-stimulated HOS cells. The results of the present study suggest, therefore, that interaction between HA and HOS cell surface integrin αV molecule may activate eNOS to catalyze NO production which, in turn, may regulate the cell proliferation in an autocrine fashion.

scholarly journals Cell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid

1998 ◽  
Vol 336 (2) ◽  
pp. 451-459 ◽  
Author(s):  
Hanne S. FINSTAD ◽  
Christian A. DREVON ◽  
Mari Ann KULSETH ◽  
Anne V. SYNSTAD ◽  
Eirunn KNUDSEN ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Eicosapentaenoic Acid ◽  
Lipid Droplets ◽  
Lipid Peroxide ◽  
Cell Cycle Distribution ◽  
Monocytic Differentiation ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Inhibition Of Proliferation ◽  
In Cells

The monocytic cell line U937-1 was cultured in the presence of eicosapentaenoic acid (20:5, n-3) (EPA) or oleic acid (18:1, n-9) (OA). EPA caused a dose-dependent inhibition of cell proliferation, whereas OA had no effect. At the highest EPA concentrations, 120 and 240 µM, inhibition of cell proliferation was accompanied by initiation of apoptosis. A concentration of 60 µM EPA caused a 35% reduction in cell proliferation without inducing apoptosis, and was therefore used for further studies. Addition of antioxidants or inhibitors of eicosanoid synthesis had no influence on the reduced cell proliferation after EPA treatment. The inhibition required continuous presence of EPA in the incubation medium as the cells resumed a normal proliferation rate when they were placed in EPA-free medium. The inhibition of proliferation was not accompanied by differentiation into macrophage-like cells, as expression of serglycin and the ability to perform respiratory burst was unaffected by EPA. Expression of CD23 mRNA increased when the cells were incubated with EPA, but to a smaller extent than after retinoic acid (RA) or PMA treatment. Furthermore, expression of the monocytic differentiation markers CD36 and CD68 was lower in cells treated with EPA or OA when compared with untreated cells. The cell cycle distribution of U937-1 cells was similar in cells incubated with EPA or PMA, whereas RA-treated cells accumulated in the G1 phase. Side scatter increased in cells incubated with EPA and OA, which was ascribed to an accumulation of lipid droplets after examination of the cells by electron microscopy. The number of droplets per cell was higher in cells exposed to EPA than OA. The cellular triacylglycerol (TAG) increased 5.5- and 15.5-fold after incubation with OA and EPA respectively. No difference in the cellular content of cholesterol compared with untreated cells was observed. The TAG fraction in EPA-treated cells contained high amounts of EPA and docosapentaenoic acid and minor amounts of docosahexaenoic acid, whereas OA-treated cells had high levels of OA in the TAG. In cells incubated with a sulphur-substituted EPA, only minor effects on cell proliferation and no accumulation of cellular TAG were observed. These findings may indicate the existence of other mechanisms for regulation of cell behaviour by very-long-chain polyunsaturated n-3 fatty acids than the well established lipid peroxide and eicosanoid pathways.

scholarly journals CircRNA8924 Promotes Cervical Cancer Cell Proliferation, Migration and Invasion by Competitively Binding to MiR-518d-5p /519-5p Family and Modulating the Expression of CBX8

2018 ◽  
Vol 48 (1) ◽  
pp. 173-184 ◽  
Author(s):  
Jiamei Liu ◽  
Danbo Wang ◽  
Zaiqiu Long ◽  
Jing Liu ◽  
Weishan Li
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Myometrial Invasion ◽  
Expression Level ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues

Background/Aims: Circular RNAs (circRNAs) play a significant role in the development and progression of various human cancers. However, the expression and function of circRNAs in cervical cancer (CC) have rarely been explored. The aim of this study was to investigate the biological function of circRNA8924 in CC and elucidate the possible molecular mechanism involved. Methods: Quantitative polymerase chain reaction was used to determine mRNA expression of circRNA8924, miR-518d-5p/519-5p and CBX8 in CC tissues and cells. CBX8 protein expression was measured by Western blotting. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay to determine cell migration and invasion. The luciferase reporter assay was used to determine the direct regulation of miR-518d-5p/519-5p and circRNA8924 or CBX8 Results: The study demonstrated that the expression level of circRNA8924 in CC was significantly higher than that in the adjacent normal tissues (P < 0.001), and that it was also associated with tumor size, FIGO staging and myometrial invasion. The knockdown of circRNA8924 significantly inhibited the proliferation, migration and invasion of CC cells SiHa and HeLa. The expression level of miR-518d-5p/519-5p was negatively correlated with circRNA8924, and circRNA8924 regulated CBX8 by competitively binding to miR-518d-5p/519-5p. Conclusions: CircRNA8924 is highly expressed in CC tissue and can be considered a competitive endogenous RNA of the miR-518d-5p/519-5p family to promote the malignant biological behavior of CC cells. It is suggested that it may serve as a new biomarker for CC diagnosis and disease progression and provide potential targets for targeted therapy.

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