Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Liu, Wanlin; Zhao, Zhenqun; Na, Yuyan; Meng, Chenyang; Wang, Jianzhong; Bai, Rui

doi:10.3892/ijmm.2018.3412

Cited by 46 publications

(52 citation statements)

References 46 publications

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“…Secondly, DUSP1 is sensitive to oxidative stress, and the phosphatase activity can be reduced. Notably, oxidative stress can be cause or consequence of the disease, and GCs themselves can contribute to the production of oxidative stress (96). Thus, although we may find techniques to increase DUSP1 abundance, it may be non-functional due to oxidation.…”

Section: Dusp1: a Therapeutic Target?mentioning

confidence: 99%

Role of Dual-Specificity Phosphatase 1 in Glucocorticoid-Driven Anti-inflammatory Responses

Hoppstädter

Ammit

2019

Front. Immunol.

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Glucocorticoids (GCs) potently inhibit pro-inflammatory responses and are widely used for the treatment of inflammatory diseases, such as allergies, autoimmune disorders, and asthma. Dual-specificity phosphatase 1 (DUSP1), also known as mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), exerts its effects by dephosphorylation of MAPKs, i.e., extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Endogenous DUSP1 expression is tightly regulated at multiple levels, involving both transcriptional and post-transcriptional mechanisms. DUSP1 has emerged as a central mediator in the resolution of inflammation, and upregulation of DUSP1 by GCs has been suggested to be a key mechanism of GC actions. In this review, we discuss the impact of DUSP1 on the efficacy of GC-mediated suppression of inflammation and address the underlying mechanisms.

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Section: Dusp1: a Therapeutic Target?mentioning

confidence: 99%

Role of Dual-Specificity Phosphatase 1 in Glucocorticoid-Driven Anti-inflammatory Responses

Hoppstädter

Ammit

2019

Front. Immunol.

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“…Autophagy is an auto‐catabolic recycling process of eukaryotic cells that is frequently dysregulated in cancer, inflammatory diseases, autoimmune diseases, aging, etc. Our preliminary results show that SANFH is associated with autophagy, and the autophagy‐related Beclin 1 and microtubule‐associated protein 1 light chain 3 (MAP1LC3) are upregulated in osteoblasts. Primary cilia are sensitive cellular antennae that sense and transmit external signals, and coordinate the responsive mechanisms.…”

Section: Introductionmentioning

confidence: 80%

Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

Zhao

Liu

Guo

et al. 2020

Orthopaedic Surgery

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Objective: To study the role of primary cilia formation disorder and osteoblasts autophagy in the pathogenesis of steroid-induced avascular necrosis of the femoral head (SANFH).Methods: Osteoblasts were isolated from rabbit bones and treated with 1 μM Methylprednisolone for 0, 12, 24, 48, and 72 h. The Beclin1, MAP1LC3, Atg-5, Atg-12, IFT20 and OFD1 mRNAs and proteins were detected by PCR and Western blotting, and their correlation was statistically analyzed. The lengths of osteoblast cilia were measured under a laser confocal microscope, and the autophagy flux was tracked by transfecting the osteoblasts with GFP-RFP-LC3 lentivirus.Results: Methylprednisolone significantly upregulated Beclin1, MAP1LC3, Atg-5, Atg-12 and OFD1 mRNAs and proteins in a time-dependent manner, and decreased that of IFT20 (P < 0.05). In addition, the autophagy flux in the osteoblasts also increased and the ciliary length decreased in a time-dependent manner after Methylprednisolone treatment. The length of the cilia were 5.46 AE 0.11 um at 0 h, 4.08 AE 0.09 um at 12 h, 3.07 AE 0.07 um at 24 h, 2.31 AE 0.10 um at 48 h, and finally 1.15 AE 0.04 um at 72 h. Methylprednisolone treatment also affects primary cilium numbers in cultures, for 0 to 72 h. The autophagy regulatory genes, Beclin1, MAP1LC3, Atg-5 and Atg-12, were found to be negatively correlated with IFT20, with an average correlation coefficient of −0.81. A negative correlation was also found between OFD1 and IFT20, with an average correlation coefficient of −0.53. Conclusion:Methylprednisolone inhibits primary cilia formation and promotes autophagy, which could be the pathological basis of SANFH. The exact regulatory mechanism needs to be further studied in vivo.

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“…Our results support the hypothesis that dexamethasone successfully interferes with new bone formation. According to previous studies, dexamethasone is able to inhibit the production of collagen and fibronectin promoting osteoblast apoptosis and autophagy of osteoblast-like cells (38).…”

Section: Tissue Growth and Immunoreactionmentioning

confidence: 93%

Immune Response After Cochlear Implantation

et al. 2020

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A cochlear implant (CI) is an electronic device that enables hearing recovery in patients with severe to profound hearing loss. Although CIs are a successful treatment for profound hearing impairment, their effectivity may be improved by reducing damages associated with insertion of electrodes in the cochlea, thus preserving residual hearing ability. Inner ear trauma leads to inflammatory reactions altering cochlear homeostasis and reducing post-operative audiological performances and electroacoustic stimulation. Strategies to preserve residual hearing ability led to the development of medicated devices to minimize CI-induced cochlear injury. Dexamethasone-eluting electrodes recently showed positive outcomes. In previous studies by our research group, intratympanic release of dexamethasone for 14 days was able to preserve residual hearing from CI insertion trauma in a Guinea pig model. Long-term effects of dexamethasone-eluting electrodes were therefore evaluated in the same animal model. Seven Guinea pigs were bilaterally implanted with medicated rods and four were implanted with non-eluting ones. Hearing threshold audiograms were acquired prior to implantation and up to 60 days by recording compound action potentials. For each sample, we examined the amount of bone and fibrous connective tissue grown within the scala tympani in the basal turn of the cochlea, the cochleostomy healing, the neuronal density, and the correlation between electrophysiological parameters and histological results. Detection of tumor necrosis factor alpha, interleukin-6, and foreign body giant cells showed that long-term electrode implantation was not associated with an ongoing inflammation. Growth of bone and fibrous connective tissue around rods induced by CI was reduced in the scala tympani by dexamethasone release. For cochleostomy sealing, dexamethasone-treated animals showed less bone tissue growth than negative. Dexamethasone did not affect cell density in the spiral ganglion. Overall, these results support the use of dexamethasone as anti-inflammatory additive for eluting electrodes able to protect the cochlea from CI insertion trauma.

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Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Cited by 46 publications

References 46 publications

Role of Dual-Specificity Phosphatase 1 in Glucocorticoid-Driven Anti-inflammatory Responses

Role of Dual-Specificity Phosphatase 1 in Glucocorticoid-Driven Anti-inflammatory Responses

Mechanism of Methylprednisolone‐Induced Primary Cilia Formation Disorder and Autophagy in Osteoblasts

Immune Response After Cochlear Implantation

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