Dexamethasone reduces ATDC5 chondrocyte cell viability by inducing autophagy

Zhao, Yan; Zuo, Yi; Huo, Hongjun; Xiao, Yulong; Yang, Xuejun; Xin, Daqi

doi:10.3892/mmr.2014.1915

Cited by 14 publications

(14 citation statements)

References 28 publications

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“…Several studies have focused on the relationship between glucocorticoids and autophagy. It is known that GCs are able to induce autophagy in different cell types [44,45], even though the explanation of the intimate molecular mechanism by which these drugs lead to this effect is not fully clear.…”

Section: Discussionmentioning

confidence: 99%

Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia

D’Assante

Fusco

Palamaro

et al. 2017

Clinical Immunology

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Ataxia-Teleangiectasia (A-T) is a neurodegenerative disorder due to mutations in ATM gene. ATM in the nucleus ensures DNA repair, while its role in the cytosol is still poorly clarified. Abnormal autophagy has been documented in other neurodegenerative disorders, thus we evaluated whether alteration in this process may be involved in the pathogenesis of A-T by analyzing the autophagic vesicles and the genes implicated in the different stages of autophagy. Through transmission electron microscopy (TEM) and immunofluorescence analysis we observed an accumulation of APs associated with a LC3 puncta pattern, and a reduced number of ALs. We also documented an increased expression of genes involved in AP and lysosome biogenesis and function, and a decrease of Vps18 expression, involved in their vesicular trafficking and fusion. mTORC1-controlled proteins were hyperphosphorylated in A-T, in keeping with an increased mTOR inhibitory influence of autophagy. Betamethasone is able to promote the degradation of SQSTM1, a biomarker of autophagy. Collectively, our results indicate that in cells from A-T patients, the APs maturation is active, while the fusion between APs and lysosomes is inappropriate, thus implying abnormalities in the cell-clearance process. We also documented a positive effect of Betamethasone on molecules implicated in autophagosome degradation.

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Section: Discussionmentioning

confidence: 99%

Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia

D’Assante

Fusco

Palamaro

et al. 2017

Clinical Immunology

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“…The treatment of other cell types with free DX has displayed different results though the reduction in viability has been clearly shown. [43][44][45] Other authors have reported the high cytotoxicity of DS loaded in PLGA/PEG scaffolds (1 mg per scaffold) in mouse primary calvarial osteoblasts, 46 as well as free DS in human microvascular endothelial cells at concentrations lower than ours (0.1 mM) 47 while other studies have revealed similar viability percentages at low concentrations (up to 100 mM) though showing differences between different cell lines displaying an enhanced toxic effect in somatic vs. tumor cells 48 or even at higher concentrations (3 mg mL À1 ) in primary rat embryo broblasts. 49 Cell membrane damage aer treatment with the considered subcytotoxic concentration (0.5 mg mL À1 ) of NPs or drugs was evaluated by ow cytometry through the distribution of viability, apoptosis and necrosis (Table 3).…”

Section: In Vitro Biocompatibility Studiesmentioning

confidence: 99%

Dual encapsulation of hydrophobic and hydrophilic drugs in PLGA nanoparticles by a single-step method: drug delivery and cytotoxicity assays

et al. 2016

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“…Shen et al observed that DXM induced apoptosis in chondrocytes, and autophagy protected chondrocytes from glucocorticoids-induced apoptosis via ROS/Akt/FOXO3 signaling (24). Zhao et al also demonstrated that high doses of DXM reduce the ATDC5 chondrocyte cell viability by inducing autophagy (25). Therefore, in the current study, it is hypothesized that the degree of autophagy determines the protective or adverse role in DXM-induced cell injury.…”

Section: Discussionmentioning

confidence: 77%

Overactivated autophagy contributes to steroid-induced avascular necrosis of the femoral head

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Steroid-induced avascular necrosis of the femoral head (SANFH) is a mainly bilateral complication of steroid therapy that involves extensive necrosis, and frequently occurs in young and middle-aged individuals, with a high disability rate. Autophagy is an intracellular lysosomal degradation process occurring in numerous diseases. However, the effect of dexamethasone (DXM)-induced autophagy on osteoblasts is unclear. The aim of the present study was to investigate the effects of autophagy on SANFH. In the present study, femoral head of SANFH patients was collected, and the autophagy in the samples was evaluated. In addition, cell proliferation, membrane integrity and differentiation of osteoblasts were also detected to confirm the effect of DXM on a mouse osteoblasts cell MC3T3-E1 in vitro. Beclin 1 and microtubule-associated protein 1 light chain 3 were used as the markers of autophagy, while the autophagy inhibitor 3-methyladenine (3-MA) was used to investigate the role of autophagy in DXM-challenged osteoblasts. Immunohistochemistry results demonstrated that Beclin1 was markedly increased in the femoral head of SANFH patients. Furthermore, the treatment of osteoblasts with DXM decreased cell viability, increased lactate dehydrogenase activity in the cell culture supernatant, and reduced the alkaline phosphatase activity and bone morphogenetic protein-2 expression in osteoblasts in vitro. By contrast, 3-MA treatment attenuated the cell injury induced by DXM. The present study indicates that overactivated autophagy may be an important factor contributing to SANFH, and autophagy may be a potential target for the prevention of SANFH.

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Dexamethasone reduces ATDC5 chondrocyte cell viability by inducing autophagy

Cited by 14 publications

References 28 publications

Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia

Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia

Dual encapsulation of hydrophobic and hydrophilic drugs in PLGA nanoparticles by a single-step method: drug delivery and cytotoxicity assays

Overactivated autophagy contributes to steroid-induced avascular necrosis of the femoral head

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