title: Roles of PKR in differentiation and apoptosis of bone-related cells.
abstract: Double-stranded RNA-dependent protein kinase (PKR) is a serine/threonine protein kinase which is activated by double-stranded RNAs and related to several signal transduction pathways. To examine the effects of PKR on bone metabolism, we established PKR-K/R mutant cells in which amino acid lysine at 296 is substituted with arginine. PKR regulated apoptosis in osteoblastic cells via nuclear factor kappa-B (NF-κB) cascade. MC3T3-E1 cells cultured with osteoblast differentiation medium differentiated into osteoblasts, while the mutant cells did not differentiate into osteoblasts. RAW246.7 cells triggered with receptor activator of NF-κB ligand (RANKL) formed tartrate-resistant acid phosphatase-positive multinucleated giant cells, whereas PKR-K/R mutant RAW cells did not. Differentiation of osteoblasts and osteoclasts was caused by NF-κB activation and signal transducer and activator of transcription 1 (STAT1) ubiquitination and degradation. We also demonstrated involvement of PKR in chondrocyte differentiation. PKR prevented tumor necrosis factor-α- and interleukin 1α-induced bone resorption in calvaria and artificially induced periodontal disease in rat. Our findings indicate that PKR regulates bone metabolism in vitro and in vivo.
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, 770-8504, Japan. tat-hane@tokushima-u.ac.jp.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Haneji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D053582:Interleukin-1alpha / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D053245:RANK Ligand; D000067996:RAW 264.7 Cells; D051381:Rats; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019892:eIF-2 Kinase / Q000502:physiology*
chemical_list: D053582:Interleukin-1alpha; D016328:NF-kappa B; D053245:RANK Ligand; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D019892:eIF-2 Kinase
keywords: Chondrocytes; Osteoblasts; Osteoclasts; PKR; Periodontal disease