Double stranded RNA-dependent protein kinase is involved in osteoclast differentiation of RAW264.7 cells in vitro

Teramachi, Junpei; Morimoto, Hiroyuki; Baba, Ryoko; Doi, Yoshiaki; Hirashima, Kanji; Haneji, Tatsuji

doi:10.1016/j.yexcr.2010.08.006

Cited by 13 publications

(19 citation statements)

References 41 publications

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“…These transcription factors drive the expression of their downstream genes and activate the differentiation of progenitor cells into osteoclast precursor. Meanwhile, Fos‐dependent IFN‐β negatively regulates the osteoclastogenesis via the IFN‐stimulated genes such as PKR [18–19]. IFN‐β also induced miR‐155, which inhibited osteoclast differentiation by targeting SOCS1 and MITF, two positive regulators induced by RNAKL and M‐CSF and play important roles in osteoclastogenesis (Fig.…”

Section: Resultsmentioning

confidence: 96%

Interferon‐β‐induced miR‐155 inhibits osteoclast differentiation by targeting SOCS1 and MITF

et al. 2012

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Edited by Zhijie ChangKeywords: microRNA miR-155 IFN-b Osteoclast differentiation SOCS1 MITF a b s t r a c t IFN-b is induced via a c-fos dependent mechanism that is present downstream of the receptor activator of NF-jB ligand (RANKL)-RANK signal transduction cascade during osteoclast differentiation. Increased production of IFN-b in turn inhibits osteoclastogenesis. However, the mechanism by which IFN-b exerts its suppressive function remains unclear. In the present study, we found that miR-155, an IFN-b-induced miRNA, mediated the suppressive effect of IFN-b on osteoclast differentiation by targeting SOCS1 and MITF, two essential regulators of osteoclastogenesis. These findings have not only demonstrated that miR-155 inhibits osteoclast differentiation, but also provided a new therapeutic target for treatment of osteoclast-mediated diseases.

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Section: Resultsmentioning

confidence: 96%

Interferon‐β‐induced miR‐155 inhibits osteoclast differentiation by targeting SOCS1 and MITF

et al. 2012

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“…Phosphorylation of IκBα plays important roles in osteoclastogenesis, osteoclast recruitment and osteolysis (45,47,48). We previously reported that OA induced apoptosis in osteoblastic cells (7,27–31).…”

Section: Discussionmentioning

confidence: 99%

Okadaic acid activates the PKR pathway and induces apoptosis through PKR stimulation in MG63 osteoblast-like cells

Haneji

Hirashima

Teramachi

et al. 2013

International Journal of Oncology

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Double-stranded RNA-dependent protein kinase (PKR) is one of the players in the cellular antiviral responses and is involved in transcriptional stimulation through activation of NF-κB. Treatment of the human osteosarcoma cell line MG63 with the protein phosphatase inhibitor okadaic acid stimulated the expression and phosphorylation of IκBα, as judged from the results of real-time PCR and western blot analysis. We investigated the functional relationship between PKR and signal transduction of NF-κB by establishing PKR-K/R cells that produced a catalytically inactive mutant of PKR. Phosphorylation of eIF-2α, a substrate of PKR, was not stimulated by okadaic acid in the PKR-K/R cells, whereas okadaic acid induced phosphorylation of eIF-2α in MG63 cells. Phosphorylation of NF-κB in MG63 cells was stimulated by okadaic acid; however, okadaic acid did not induce phosphorylation of NF-κB in the PKR-K/R cells. Finally, okadaic acid-induced apoptosis was inhibited in the PKR-K/R cells. Our results suggest that okadaic acid-induced phosphorylation of IκBα was mediated by PKR kinase activity, thus, indicating the involvement of this kinase in the control mechanism governing the activation of NF-κB and induction of apoptosis.

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“…ISGylation affects the nuclear factor-kappa B (NF-κB) signaling pathway as well as the activity of doublestranded RNA-activated protein kinase, 5,6) both of which have important roles in osteoclastogenic differentiation. 7,8) Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells derived from monocyte/macrophage lineage cells. 7,9) Receptor activator of nuclear factor-κB ligand (RANKL) is essential for the induction of osteoclastogenesis.…”

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ISG15 Regulates RANKL-Induced Osteoclastogenic Differentiation of RAW264 Cells

Takeuchi

Shimakawa

Tamura

et al. 2015

Biological & Pharmaceutical Bulletin

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Interferon-stimulated gene 15 kDa (ISG15) is a protein upregulated by interferon-β that negatively regulates osteoclastogenesis. We investigated the role of ISG15 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells. RANKL stimulation induced ISG15 expression in RAW264 cells at both the mRNA and protein levels. Overexpression of ISG15 in RAW264 cells resulted in suppression of cell fusion in RANKL-stimulated cells as well as the reduced expression of ATP6v0d2, a gene essential for cell fusion in osteoclastogenic differentiation. These results suggest that ISG15 suppresses RANKL-induced osteoclastogenesis, at least in part, through inhibition of ATP6v0d2 expression.Key words interferon-stimulated gene 15 kDa (ISG15); osteoclast; interferon; receptor activator of nuclear factor-κB ligand (RANKL); RAW264; ATP6v0d2Interferon-α/β is a multifunctional cytokine that exerts various biological functions in immunity, cell differentiation, and so on via the induction of downstream genes called interferonstimulated genes (ISGs).1,2) Interferon-stimulated gene 15 kDa (ISG15), a ubiquitin-like protein, is one of the proteins that are most upregulated by interferon stimulation.3,4) Upon stimulation of the cells with interferon or pathogenic materials such as lipopolysaccharides, the expression of ISG15 and several other enzymes that catalyze protein modification with ISG15 (ISGylation) is induced, followed by the ISGylation of various cellular proteins. ISGylation affects the nuclear factor-kappa B (NF-κB) signaling pathway as well as the activity of doublestranded RNA-activated protein kinase, 5,6) both of which have important roles in osteoclastogenic differentiation. 7,8) Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells derived from monocyte/macrophage lineage cells. 7,9) Receptor activator of nuclear factor-κB ligand (RANKL) is essential for the induction of osteoclastogenesis.10) The murine RAW264 cell line is a useful model of osteoclastogenesis as, upon stimulation with RANKL, RAW264 cells differentiate into TRAP-positive mononuclear cells, which subsequently undergo cell fusion to form TRAPpositive multinuclear osteoclasts. In vivo, osteoclastogenesis is tightly controlled by factors produced from cells such as osteoblasts and osteocytes, and deregulation of osteoclastogenesis results in various diseases such as osteoporosis. 7,9,11,12)

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Double stranded RNA-dependent protein kinase is involved in osteoclast differentiation of RAW264.7 cells in vitro

Cited by 13 publications

References 41 publications

Interferon‐β‐induced miR‐155 inhibits osteoclast differentiation by targeting SOCS1 and MITF

Interferon‐β‐induced miR‐155 inhibits osteoclast differentiation by targeting SOCS1 and MITF

Okadaic acid activates the PKR pathway and induces apoptosis through PKR stimulation in MG63 osteoblast-like cells

ISG15 Regulates RANKL-Induced Osteoclastogenic Differentiation of RAW264 Cells

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