Effect of interferon-γ on the fusion of mononuclear osteoclasts into bone-resorbing osteoclasts

Kim, Jeung Woo; Lee, Myeung Su; Lee, Chang Hoon; Kim, Ha Young; Chae, Soo Uk; Kwak, Han Bok; Oh, Jae Min

doi:10.5483/bmbrep.2012.45.5.281

Cited by 30 publications

(19 citation statements)

References 29 publications

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“…IFN‐γ could either suppress osteoclastogenesis by inhibiting RANK signaling, or stimulate OC formation and bone loss in vivo through stimulating antigen‐dependent T‐cell activation and T‐cell secretion of RANKL and TNF‐α . IFN‐γ also increased the fusion and bone resorption ability of OCs from pre‐fusion OCs . In this study, we found that IFN‐γ induced the immunosuppressive function of human OCs through IDO.…”

Section: Discussionmentioning

confidence: 55%

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Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell–Derived IFN-γ and CD40 Ligand In Vitro

Qian

et al. 2014

Journal of Bone and Mineral Research

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Osteoclasts (OCs) are bone resorbing cells whose activity can be regulated by activated T cells and their cytokines. However, the immune function of OCs is largely unknown. In this study, we found that as bystanders, human OCs effectively suppressed T-cell proliferation induced by allogeneic, microbial antigenic and T-cell receptor stimuli in vitro. Mechanistic studies revealed that T cell-derived IFN-γ and CD40 ligand (CD40L) induced the expression of indoleamine 2,3-dioxygenase (IDO) in OCs, which mediated the immunosuppressive function on T-cell proliferation through depleting tryptophan. Neutralizing IFN-γ and blocking CD40L, and silencing or inhibiting IDO in OCs restored T-cell proliferation in the presence of OCs. Our data reveal a novel function of human OCs as inducible immunosuppressive cells, and a feedback loop between OCs and activated T cells. Thus, this study provides new insight into the mechanism of the immunosuppressive function of OCs, and may be helpful for developing novel therapeutic strategies for human diseases involving both the bone and immune systems.

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Section: Discussionmentioning

confidence: 55%

“…(35) IFN-g also increased the fusion and bone resorption ability of OCs from pre-fusion OCs. (36) In this study, we found that IFN-g induced the immunosuppressive function of human OCs through IDO. In the murine study from M. Nakamura's laboratory, it was shown that OC precursors express IFNGR.…”

Section: Discussionmentioning

confidence: 57%

Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell–Derived IFN-γ and CD40 Ligand In Vitro

Qian

et al. 2014

Journal of Bone and Mineral Research

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“…Interestingly, the inhibitory action of IFN-γ in osteoclastogenesis acts cooperatively with the TLR signaling pathways by downregulating RANK and c-Fms expression in OC precursors ( 96 ). In contrast to these findings, IFN-γ has a positive role in osteoclastogenesis under specific pathophysiological conditions ( 97 98 99 ). The loss of IFN-γ expression has been implicated in protection against infection-induced bone destruction in IFN-γ-deficient mice ( 97 ).…”

Section: Anti-osteoclastogenic Cytokinesmentioning

confidence: 74%

Regulation of Osteoclast Differentiation by Cytokine Networks

et al. 2018

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Cytokines play a pivotal role in maintaining bone homeostasis. Osteoclasts (OCs), the sole bone resorbing cells, are regulated by numerous cytokines. Macrophage colony-stimulating factor and receptor activator of NF-κB ligand play a central role in OC differentiation, which is also termed osteoclastogenesis. Osteoclastogenic cytokines, including tumor necrosis factor-α, IL-1, IL-6, IL-7, IL-8, IL-11, IL-15, IL-17, IL-23, and IL-34, promote OC differentiation, whereas anti-osteoclastogenic cytokines, including interferon (IFN)-α, IFN-β, IFN-γ, IL-3, IL-4, IL-10, IL-12, IL-27, and IL-33, downregulate OC differentiation. Therefore, dynamic regulation of osteoclastogenic and anti-osteoclastogenic cytokines is important in maintaining the balance between bone-resorbing OCs and bone-forming osteoblasts (OBs), which eventually affects bone integrity. This review outlines the osteoclastogenic and anti-osteoclastogenic properties of cytokines with regard to osteoimmunology, and summarizes our current understanding of the roles these cytokines play in osteoclastogenesis.

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“…The method also affects wound perfusion, growth factor, cytokine expression and cellular activity. These roles lead to enhanced granulation tissue formation and improved wound healing parameters (6)(7)(8). Therefore, the treatment should be focused on inducing osteogenesis through the effects of mechanical stimulation and growth factors in order to increase the early blood supply and restart bone healing (9).…”

Section: Discussionmentioning

confidence: 99%

Functions and mechanisms of intermittent negative pressure for osteogenesis in human bone marrow mesenchymal stem cells

Yang

Zhang

et al. 2014

Molecular Medicine Reports

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The present study aimed to determine the mechanism by which low‑intensity intermittent negative pressure affects the differentiation and proliferation of human mesenchymal stem cells (MSCs). Alkaline phosphatase (ALP) activity, type I collagen and vascular endothelial growth factor (VEGF) were detected to analyze differentiation. MTT and flow cytometry were employed to measure proliferation and apoptosis. Western blot analysis was used to examine endoplasmic reticulum (ER) stress‑associated factors. This study was divided into two groups, including a normal group (without any treatment) and vacuum group (treated with a vacuum). There was a significant decrease in the proliferation of cells in the vacuum group. The number of cells in S phase was reduced significantly, while the rate of apoptosis and the activity of ALP were markedly increased under vacuum conditions. Expression of collagen type I and VEGF was significantly increased, and the ratio of osteoprotegrin to osteoprotegrin ligand was decreased significantly in the vacuum group. ER stress‑associated proteins, p‑PRKR‑like ER kinase, inositol‑requiring enzyme 1 and cleaved activating transcription factor 6, as well as the downstream factors, were activated when treated with negative pressure. In conclusion, treatment with low‑intensity and intermittent negative pressure may inhibit the proliferation of MSCs and trigger ER stress‑associated cellular apoptosis, further enhancing osteogenesis activity and inducing differentiation to osteoblasts.

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Effect of interferon-γ on the fusion of mononuclear osteoclasts into bone-resorbing osteoclasts

Cited by 30 publications

References 29 publications

Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell–Derived IFN-γ and CD40 Ligand In Vitro

Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell–Derived IFN-γ and CD40 Ligand In Vitro

Regulation of Osteoclast Differentiation by Cytokine Networks

Functions and mechanisms of intermittent negative pressure for osteogenesis in human bone marrow mesenchymal stem cells

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