Costimulation of Murine Osteoblasts with Interferon-γand Tumor Necrosis Factor-αInduces Apoptosis through Downregulation of Bcl-2 and Release of Cytochromecfrom Mitochondria

Iguchi, Mayumi; Hiroi, Miki; Kanegae, Haruhide; Ohmori, Yoshihiro

doi:10.1155/2018/3979606

Cited by 22 publications

(17 citation statements)

References 75 publications

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“…It can be imagined that the production of ROS mediated by mitochondria under oxidative stress leads to chondrocyte apoptosis. ROS can directly change mitochondrial permeability, resulting in loss of mitochondrial membrane potential, reduction of ATP production [ 18 , 36 , 37 ], which was further confirmed in our experiments ( Figure 4(c) ). When pretreated with caspase inhibitor or ASP, apoptosis was ameliorated to a certain extent, ATP production increased ( Figure 4(c) ).…”

Section: Discussionsupporting

confidence: 82%

Oxidative Stress Induces Chondrocyte Apoptosis through Caspase-Dependent and Caspase-Independent Mitochondrial Pathways and the Antioxidant Mechanism of Angelica Sinensis Polysaccharide

Chen

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Introduction. Chondrocyte apoptosis is considered one of the pathogenic factors of osteoarthritis (OA), but its importance in the pathogenesis of OA remains unclear. Recent research adds progress to the knowledge that the mitochondrial signaling pathway mediates chondrocyte apoptosis in OA. Method. Rat chondrocyte exposed to H2O2 was used as the experimental oxidative stress model. Chondrocyte viability was tested by cell counting kit-8 (CCK-8) assay. Cell apoptosis and ROS were tested by flow cytometry. Contents of malondialdehyde (MDA), catalase (CAT), caspase-3, caspase-9, cytochrome C, superoxide dismutase (SOD)-2, and adenosine triphosphate (ATP) were evaluated by biochemical detection. The expressions of related genes and proteins were assessed by quantitative polymerase chain reaction (qPCR) and western blot. Results. H2O2 provokes oxidative stress and decreases the viability of chondrocyte, which leads to the release of cytochrome C and inhibition of SOD-2 activity. The damage of mitochondrion disturbs the energy metabolism of chondrocyte and eventually induces chondrocyte apoptosis through the mitochondrial pathway. Furthermore, pretreated with anglicasinensis polysaccharide (ASP) or caspase inhibitors increase the expression of Bcl-2 and Bcl-xL but do not work for the expression of Bax and Bad. Conclusion. Oxidative stress induces chondrocyte apoptosis through caspase-dependent and caspase-independent mitochondrial pathways. ASP protects chondrocyte from H2O2-induced oxidative stress and subsequent cell injury through its antioxidant effect by inhibiting the caspase pathway.

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Section: Discussionsupporting

confidence: 82%

Oxidative Stress Induces Chondrocyte Apoptosis through Caspase-Dependent and Caspase-Independent Mitochondrial Pathways and the Antioxidant Mechanism of Angelica Sinensis Polysaccharide

Chen

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Moreover, IFN-γ receptor-deficient mice exhibit decreased OB differentiation capacity [ 87 ]. However, it has also been reported that IFN-γ and TNF-α synergistically promote OB apoptosis by inducing nitric oxide production or mitochondrial cytochrome c release, downregulating B cell lymphoma 2 expression and activating caspases [ 152 , 153 ]. IFN-α inhibits OB progenitor proliferation and differentiation by inhibiting ALP activity and downregulating BMP-2 expression [ 116 ].…”

Section: Cytokine Regulation Of Osteoblastogenesismentioning

confidence: 99%

Regulation of Osteoblast Differentiation by Cytokine Networks

Amarasekara

Kim

Rho

2021

IJMS

163

137

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Osteoblasts, which are bone-forming cells, play pivotal roles in bone modeling and remodeling. Osteoblast differentiation, also known as osteoblastogenesis, is orchestrated by transcription factors, such as runt-related transcription factor 1/2, osterix, activating transcription factor 4, special AT-rich sequence-binding protein 2 and activator protein-1. Osteoblastogenesis is regulated by a network of cytokines under physiological and pathophysiological conditions. Osteoblastogenic cytokines, such as interleukin-10 (IL-10), IL-11, IL-18, interferon-γ (IFN-γ), cardiotrophin-1 and oncostatin M, promote osteoblastogenesis, whereas anti-osteoblastogenic cytokines, such as tumor necrosis factor-α (TNF-α), TNF-β, IL-1α, IL-4, IL-7, IL-12, IL-13, IL-23, IFN-α, IFN-β, leukemia inhibitory factor, cardiotrophin-like cytokine, and ciliary neurotrophic factor, downregulate osteoblastogenesis. Although there are gaps in the body of knowledge regarding the interplay of cytokine networks in osteoblastogenesis, cytokines appear to be potential therapeutic targets in bone-related diseases. Thus, in this study, we review and discuss our osteoblast, osteoblast differentiation, osteoblastogenesis, cytokines, signaling pathway of cytokine networks in osteoblastogenesis.

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“…The release of cytochrome c was inhibited by the antiapoptotic members of the Bcl-2 family and stimulated by the proapoptotic members, such as Bax. Cytochrome c promoted the formation of the apoptosome by recruiting caspase-9, which then induced caspase-3 activation and triggered the caspase cascade, eventually causing the cell apoptotic death [26–28].…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress

Huang

Shen

et al. 2019

Oxidative Medicine and Cellular Longevity

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Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

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Costimulation of Murine Osteoblasts with Interferon-γand Tumor Necrosis Factor-αInduces Apoptosis through Downregulation of Bcl-2 and Release of Cytochromecfrom Mitochondria

Cited by 22 publications

References 75 publications

Oxidative Stress Induces Chondrocyte Apoptosis through Caspase-Dependent and Caspase-Independent Mitochondrial Pathways and the Antioxidant Mechanism of Angelica Sinensis Polysaccharide

Oxidative Stress Induces Chondrocyte Apoptosis through Caspase-Dependent and Caspase-Independent Mitochondrial Pathways and the Antioxidant Mechanism of Angelica Sinensis Polysaccharide

Regulation of Osteoblast Differentiation by Cytokine Networks

Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress

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