2011 Fiscal Year Final Research Report
The role of PKR, Osterix, and Calcineurin in osteogenesis
| Project/Area Number |
21592330
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HANEJI Tatsuji 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (50156379)
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| Co-Investigator(Kenkyū-buntansha) |
TERAMACHI Jyumpei 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (20515986)
NAKASHIMA Yoshiki 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (30593082)
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| Co-Investigator(Renkei-kenkyūsha) |
MORIMOTO Hiroyuki 産業医科大学, 医学部, 准教授 (30335806)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 蛋白質脱リン酸化 / 蛋白質リン酸化 / 破骨細胞 / 骨吸収 / 軟骨細胞 / PKR |
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| Research Abstract |
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.
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