What question did this study set out to answer?

To determine whether depleting phosphoglycerate kinase 1 (PGK1) activates the Keap1-Nrf2 signaling cascade to protect human osteoblasts from dexamethasone-induced oxidative damage and cell death.

November 26, 2019Cell Death and DiseaseOpen Access

PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone

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To determine whether depleting phosphoglycerate kinase 1 (PGK1) activates the Keap1-Nrf2 signaling cascade to protect human osteoblasts from dexamethasone-induced oxidative damage and cell death.
Targeted shRNA and CRISPR/Cas9 were used to silence or knock out PGK1 in OB-6 osteoblastic cells and primary human osteoblasts exposed to dexamethasone.
Nrf2 signaling activity was evaluated by measuring Nrf2 protein stabilization, nuclear translocation, and downstream antioxidant response element-dependent gene expression (HO1, NQO1, GCLC).
Human necrotic femoral head tissues from patients taking dexamethasone were analyzed to assess PGK1 and HO1 expression.
PGK1 silencing or knockout stabilized Nrf2, promoted its nuclear translocation, increased HO1, NQO1, and GCLC expression, and significantly reduced dexamethasone-induced oxidative stress and cell death.
The protective cytoprotective effect of PGK1 knockdown against dexamethasone was abolished by co-silencing Nrf2 and mimicked by Keap1 knockdown.
PGK1 expression was significantly downregulated alongside HO1 in necrotic femoral head tissues obtained from dexamethasone-treated patients.

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Implication

In vitro experimental study demonstrates PGK1 depletion protects osteoblasts from dexamethasone toxicity, indicating a therapeutic target for steroid-induced necrosis.

Cite This Study

Liang et al. (2019) studied this question.

synapsesocial.com/papers/6a1bf06e412da96b219cd371 https://doi.org/10.1038/s41419-019-2112-1

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Implication

In vitro experimental study demonstrates PGK1 depletion protects osteoblasts from dexamethasone toxicity, indicating a therapeutic target for steroid-induced necrosis.

PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone

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Implication

Cite This Study

PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone

Key Points

Discussion

Implication

Cite This Study

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