The role of PKR, Osterix, and Calcineurin in osteogenesis

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A dominant-negative mutant PKR cDNA, in which the amino acid lysine at 296 was replaced with arginine, was transfected into RAW264. 7 cells. RANKL stimulated the TRAP-positive multinuclear cell formation in RAW264. 7 cells. However, TRAP-positive multinuclear cells were not formed in the PKR-K/ R mutant cells even when the cells were stimulated with higher doses of RANKL. A specific inhibitor of PKR, 2-aminopurine, also suppressed the RANKL-induced osteoclast differentiation in RAW264. 7 cells. Immunohistochemical study shows that PKR localized in osteoclasts of metatarsal bone of newborn mouse.ATDC-5 cells differentiated into chondrocytes by the insulin-treatment and the cells produced Alcian blue-positive cartilage matrix. When the cells were treated with 2-aminopurine, formation of cartilage matrix decreased in a dose dependent manner. Protein expression of STAT1, Osterix, and Sox-9 showed different manners during chondrogenesis. We also showed that PKR localized in a marginal region of mandibular condyle cartilage in mouse embryo.Our findings suggest that PKR plays important roles in the differentiation of osteoclasts and chondrocytes by modulating STAT1, OSX, and Sox-9 expressions.