Benzo[a]pyrene exposure promotes RIP1-mediated necroptotic death of osteocytes and the JNK/IL-18 pathway activation via generation of reactive oxygen species

Zhang, Tao; Shen, Yuchen; Zhu, Ruirong; Shan, Weiyan; Li, Yurong; Yan, Ming; Zhang, Yun

doi:10.1016/j.tox.2022.153244

Cited by 9 publications

(4 citation statements)

References 43 publications

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“…Emerging evidence has demonstrated that osteocytes death by apoptosis is implicated in certain pathological conditions, such as aging, estrogen deficiency, androgens deletion, excessive glucocorticoids, mechanical unloading and overloaded orthodontic force (Farr et al, 2017; Huber et al, 2007; Rony et al, 2019; Storlino et al, 2020), which reduces osteoblastic bone formation and increases osteoclastic bone resorption, ultimately resulting in osteoporosis and increasing the risk of fracture. Recently, our findings also have shown that environmental pollutants BPA and BaP remarkably trigger apoptosis of osteocytes in vitro or in vivo (Zhang et al, 2021; Zhang et al, 2022), which later produces interleukin (IL)‐1β and IL‐18 for the attachment and differentiation of osteoclasts to cause bone destruction (Yang et al, 2022). Based on these observations, we speculate that osteocytes apoptosis may be the adverse effect of environmental pollutants on bone metabolism and skeleton growth.…”

Section: Introductionmentioning

confidence: 81%

“…Except for the degradation of nuclear DNA, mitochondrial impairment has been identified to be involved in apoptosis (Yang et al, 2019; Yang et al, 2019). BPS exposure to human neuroblastoma cells, TM3 mouse Leydig cells and SK‐N‐SH cells targets the inner mitochondrial membrane and opens mitochondrial permeability transition pore (mPTP), which results in loss of MMP, outer membrane rupture and a series of apoptotic responses (He et al, 2021; Wang et al, 2021; Wang et al, 2021; Zhang et al, 2022). To confirm mitochondrial alterations in the process of apoptotic cell death caused by BPS, we observed the levels of MMP and morphological changes in mitochondria in MLO‐Y4 cells.…”

Section: Discussionmentioning

confidence: 99%

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Bisphenol S exposure promotes cell apoptosis and mitophagy in murine osteocytes by regulating mtROS signaling

Shan

Niu

Lin

et al. 2023

Microscopy Res & Technique

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Bisphenol S (BPS), a safer alternative to bisphenol A, is commonly used as a plasticizer to manufacture various food-packaging materials. The accumulated BPS inhibits osteoblastic bone formation and promotes osteoclastogenesis, thereby accelerating remarkable bone destruction, but it is unclear whether BPS affects osteocytes, comprising over 95% of all bone cells. This study aimed to investigate the biological effect of BPS on osteocytes in vitro, as well as the detailed mechanism. Results showed that BPS (200, 400 μmol/L) exposure caused dose-dependently cell death of osteocytes MLO-Y4, and increased cell apoptosis. BPS induced loss of mitochondrial membrane potential (MMP) and mitochondria impairment. Furthermore, BPS upregulated expressions of mitophagy-related proteins including microtubule-associated protein light chain 3 (LC-3) II and PTEN-induced putative kinase (PINK) 1, accompanied by elevation of autophagy flux and the accumulation of acidic vacuoles; whereas p62 level was downregulated after BPS treatment. Additionally, BPS triggered the production of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS), while it decreased expression levels of nuclear factor E2-related factor 2 (Nrf2) and quinone oxidoreductase 1 (NQO1). The specific mtROS scavenger Mito-TEMPO reversed cell apoptosis and mitophagy, suggesting that mtROS contributes to BPS exposure-induced apoptosis and mitophagy in MLO-Y4 cells. Our data first provide novel evidence that apoptosis and mitophagy as cellular mechanisms for the toxic effect of BPS on osteocytes, thereby helping our understanding of the potential role of osteocytes in the adverse effect of BPS and its analogs on bone growth, and supporting strategies targeting bone destruction caused by BPS.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Bisphenol S exposure promotes cell apoptosis and mitophagy in murine osteocytes by regulating mtROS signaling

Shan

Niu

Lin

et al. 2023

Microscopy Res & Technique

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“…The tissues were then serial mesiodistal sectioned longitudinally at a thickness of 6 μm and mounted on polylysine-coated glass slides. For histological analysis, hematoxylin and eosin (H&E) staining was performed on selected sections as previously described (Zhang et al, 2022). The stained sections were imaged using a Leica DM3000 microscope (Leica, Wetzlar, Germany) equipped with a digital camera.…”

Section: Hematoxylin and Eosin Stainingmentioning

confidence: 99%

Reactive oxygen species‐mediated endoplasmic reticulum stress contributes to osteocyte death induced by orthodontic compressive force

Yan

Zhang

Niu

et al. 2023

Microscopy Res & Technique

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During orthodontic tooth movement (OTM), osteocytes, the most mechanosensitive cells in alveolar bone, suffer the heavy orthodontic force and initiate alveolar bone resorption on the compression side. However, the inherent mechanisms of compressive force‐induced osteocyte death are not fully understood. In this study, we established an OTM model on Sprague–Dawley rats by inserting coil springs to investigate osteocyte damage on the compression side of alveolar bone. We then applied compressive force on the MLO‐Y4 osteocyte‐like cell line in vitro to explore whether the reactive oxygen species (ROS)‐mediated endoplasmic reticulum stress (ERS) pathway is involved in compressive force‐induced osteocyte death. We found that the orthodontic force caused apparent alveolar bone loss, osteocyte death, and elevated serum sclerostin and receptor activator of NF‐κB ligand (RANKL) levels in rats. In vitro, compressive force inhibited cell viability but increased the LDH leakage and loss of mitochondrial membrane potential in MLO‐Y4 cells. Simultaneously, it activated protein kinase RNA‐like endoplasmic reticulum kinase (PERK), eukaryotic translation initiation factor 2 (eIF2α), and their downstream pro‐apoptotic ERS signaling proteins and caused significant osteocyte apoptosis, which can be blocked by ERS inhibitor salubrinal. Moreover, the compressive force elevated intracellular ROS levels, while the ROS scavenger N‐acetyl‐L‐cysteine (NAC) alleviated ERS and apoptosis in loaded osteocytes. These results suggest that the orthodontic compressive force induced osteocyte apoptosis via the ROS‐mediated ERS pathway. This study first proposes the ERS pathway as a new potential pathway for regulating the rate of OTM based on osteocyte death.Research Highlights The orthodontic force increases osteocyte death in rat alveolar bone. The compressive force causes osteocyte apoptosis by the endoplasmic reticulum stress (ERS) pathway in vitro. The ROS scavenger NAC blocked compressive force‐induced ERS and osteocyte apoptosis.

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“…The increase in reactive oxygen species (ROS) induced by an intracellular oxidant such as H 2 O 2 causes persistent damage to the telomeric and mitochondrial DNA, and leads to a DNA-damage response (DDR). Consequently, the senescence-associated secretory phenotype (SASP) is increased, and the p38 mitogen-activated protein kinases (p38 MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) signaling pathways are activated with the upregulation of IL-2, IL-4, IL-6, IL-8, and TNF-α expression [ 2 , 3 ]. Thus, the skin is inevitably affected by the internal aging process, while various external environmental factors accelerate the development of skin-aging-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Umbilical Cord Mesenchymal-Stem-Cell-Derived Exosomes Exhibit Anti-Oxidant and Antiviral Effects as Cell-Free Therapies

Meng,

Li,

Liang

et al. 2023

Viruses

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The oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to cell aging and death. Equally, the skeletal muscle usually hosts enteroviral persistent infection in inflammatory muscle diseases. As excellent bioactive products, the exosomes derived from umbilical cord mesenchymal stem cells (ucMSCs) have been proven to be safe and have low immunogenicity with a potential cell-free therapeutic function. Here, exosomes derived from ucMSCs (ucMSC-EXO) were extracted and characterized. In a model of oxidative damage to skin fibroblasts (HSFs) under exposure to H2O2, ucMSC-EXO had an observable repairing effect for the HSFs suffering from oxidative damage. Furthermore, ucMSC-EXO inhibited mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) signaling pathways, thereby promoting p21 protein expression while decreasing lamin B1 protein expression, and finally alleviated oxidative stress-induced cell damage and aging. In a model of rhabdomyosarcoma (RD) cells being infected by enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the ucMSC-EXO enhanced the expression of interferon-stimulated gene 15 (ISG15) and ISG56 to inhibit enteroviral replication, whereafter reducing the virus-induced proinflammatory factor production. This study provides a promising therapeutic strategy for ucMSC-EXO in anti-oxidative stress and antiviral effects, which provides insight into extending the function of ucMSC-EXO in cell-free therapy.

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Benzo[a]pyrene exposure promotes RIP1-mediated necroptotic death of osteocytes and the JNK/IL-18 pathway activation via generation of reactive oxygen species

Cited by 9 publications

References 43 publications

Bisphenol S exposure promotes cell apoptosis and mitophagy in murine osteocytes by regulating mtROS signaling

Bisphenol S exposure promotes cell apoptosis and mitophagy in murine osteocytes by regulating mtROS signaling

Reactive oxygen species‐mediated endoplasmic reticulum stress contributes to osteocyte death induced by orthodontic compressive force

Umbilical Cord Mesenchymal-Stem-Cell-Derived Exosomes Exhibit Anti-Oxidant and Antiviral Effects as Cell-Free Therapies

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