Double Stranded RNA-Dependent Protein Kinase is Necessary for TNF-α-Induced Osteoclast Formation In Vitro and In Vivo

Journal of Cellular Biochemistry
Hiroki ShinoharaTatsuji Haneji

Abstract

Double-stranded RNA-dependent protein kinase (PKR) is involved in cell cycle progression, cell proliferation, cell differentiation, tumorgenesis, and apoptosis. We previously reported that PKR is required for differentiation and calcification in osteoblasts. TNF-α plays a key role in osteoclast differentiation. However, it is unknown about the roles of PKR in the TNF-α-induced osteoclast differentiation. The expression of PKR in osteoclast precursor RAW264.7 cells increased during TNF-α-induced osteoclastogenesis. The TNF-α-induced osteoclast differentiation in bone marrow-derived macrophages and RAW264.7 cells was markedly suppressed by the pretreatment of PKR inhibitor, 2-aminopurine (2AP), as well as gene silencing of PKR. The expression of gene markers in the differentiated osteoclasts including TRAP, Calcitonin receptor, cathepsin K, and ATP6V0d2 was also suppressed by the 2AP treatment. Bone resorption activity of TNF-α-induced osteoclasts was also supressed by 2AP treatment. Inhibition of PKR supressed the TNF-α-induced activation of NF-κB and MAPK in RAW264.7 cells. 2AP inhibited both the nuclear translocation of NF-κB and its transcriptional activity in RAW264.7 cells. 2AP inhibited the TNF-α-induced expression of NFAT...Continue Reading

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Citations

Dec 18, 2016·Anatomical Science International·Tatsuji Haneji
Nov 11, 2018·Journal of Cellular Physiology·Ruohui TangJun Fei
Mar 21, 2019·Journal of Cellular and Molecular Medicine·Lingbo KongDingjun Hao
Aug 18, 2020·Cell Death and Differentiation·Han QiaoYiqun Deng
Nov 18, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Yueying Chen, Jun Shen
May 18, 2021·Frontiers in Aging Neuroscience·Nicolás W MartinezSoledad Matus

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