2003 Fiscal Year Annual Research Report

骨格形成細胞の大きさ・化学走性・分化におけるAktとRunx2の相互作用の解明

Research Project

Project/Area Number	15370087
Research Institution	Osaka University
Principal Investigator	小守壽文大阪大学, 医学系研究科, 助手 (00252677)
Keywords	Runx2 / phosphatidylinositol 3-kinase / Akt / 骨芽細胞分化 / 軟骨細胞分化 / 細胞遊走
Research Abstract	骨芽細胞系細胞MC3T3-E1の分化は、Runx2により促進、dn-Runx2により抑制されたが、Runx2による促進は、抗IGF-1抗体処理、phosphatidylinositol 3-kinase(PI3K)抑制剤LY294002処理、あるいはドミナントネガティブAkt(dn-Akt)の導入により抑制された。未分化間葉系細胞C3H10T1/2は、Runx2により骨芽細胞への分化が誘導されたが、これは、dn-Aktの導入により抑制された。さらに、インスリン存在下で軟骨細胞に分化するATDC5は、Runx2によって分化が促進されたが、これはLY294002処理、あるいはdn-Aktの導入により抑制された。Runx2はMC3T3-E1、C3H10T1/2、ATDC5の細胞遊走を促進し、dn-Runx2は抑制した。また、Runx2による細胞遊走の促進は、LY294002処理、あるいはdn-Aktの導入により抑制された。さらに、Runx2はp85、p110β、Aktの蛋白量を増加させた。これらの結果は、Runx2がPI3K-Aktシグナルと相互作用しながら、骨芽細胞・軟骨細胞分化および細胞遊走を調節していることを示している。MC3T3-E1細胞をLY294002処理すると、Runx2のDNA結合能および転写活性化能が著明に抑制された。また、ミリスチル基をつけた活性型Akt(myrAkt)は、Runx2のDNA結合能および転写活性化能を著明に促進、dn-Aktは著明に抑制した。したがって、PI3K-Aktシグナルは、Runx2のDNA結合能および転写活性化能を調節し、Runx2はPI3K-Aktの蛋白量を調整し、お互いに相互作用しながら、骨芽細胞・軟骨細胞分化および細胞遊走を調節していることが明らかとなった。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] A.Kadowaki: "Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice"Bone. (in press).
[Publications] T.Shimoaka: "Impairment of bone healing by insulin receptor substrate-1 deficiency"J.Biol.Chem.. (in press).
[Publications] Y.Ichikawa: "Evaluation of 9.4-T MR micro-imaging in assessing normal and defective fetal bone development : comparison of MR imaging and histological findings"Bone. (in press).
[Publications] S.Toyosawa: "Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia"Modern Pathol.. (in press).
[Publications] R.Fukuyama: "Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling"Biochem.Biophys.Res.Commun.. 315. 636-642 (2004)
[Publications] S.Toyosawa: "mRNA expression and protein localization of dentin matrix protein 1 during dental root formation"Bone. 34. 124-133 (2004)
[Publications] H.Enomoto: "Runx2 deficiency in chondrocytes causes adipogenic changes in vitro"J.Cell Sci.. 117. 417-425 (2004)
[Publications] J.Pratap: "Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts"Cancer Res.. 63. 5357-5362 (2003)
[Publications] H.Enomoto: "Induction of osteoclast differentiation by Runx2 through RANKL and OPG regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene"J.Biol.Chem.. 278. 23971-23977 (2004)
[Publications] M.Takamoto: "Hedgehog signaling enhances core-binding factor al and receptor activator of nuclear factor-kappaB ligand (RANKL) gene expression in chondrocytes"J.Endocrinol.. 177. 413-421 (2003)
[Publications] K.Hirata: "Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2"Bone. 32. 502-512 (2003)
[Publications] T.Komori: "Requisite roles of Runx2 and Cbfb in skeletal development"J.Bone Miner.Metab.. 21. 193-197 (2003)
[Publications] M.Iwamoto: "Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP)"Osteoarthritis Cartilage. 11. 6-15 (2003)

2003 Fiscal Year Annual Research Report

骨格形成細胞の大きさ・化学走性・分化におけるAktとRunx2の相互作用の解明

Principal Investigator

小守 壽文 大阪大学, 医学系研究科, 助手 (00252677)

Research Products

[Publications] A.Kadowaki: "Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice"Bone. (in press).

[Publications] T.Shimoaka: "Impairment of bone healing by insulin receptor substrate-1 deficiency"J.Biol.Chem.. (in press).

[Publications] Y.Ichikawa: "Evaluation of 9.4-T MR micro-imaging in assessing normal and defective fetal bone development : comparison of MR imaging and histological findings"Bone. (in press).

[Publications] S.Toyosawa: "Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia"Modern Pathol.. (in press).

[Publications] R.Fukuyama: "Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling"Biochem.Biophys.Res.Commun.. 315. 636-642 (2004)

[Publications] S.Toyosawa: "mRNA expression and protein localization of dentin matrix protein 1 during dental root formation"Bone. 34. 124-133 (2004)

[Publications] H.Enomoto: "Runx2 deficiency in chondrocytes causes adipogenic changes in vitro"J.Cell Sci.. 117. 417-425 (2004)

[Publications] J.Pratap: "Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts"Cancer Res.. 63. 5357-5362 (2003)

[Publications] H.Enomoto: "Induction of osteoclast differentiation by Runx2 through RANKL and OPG regulation and partial rescue of osteoclastogenesis in Runx2-/- mice by RANKL transgene"J.Biol.Chem.. 278. 23971-23977 (2004)

[Publications] M.Takamoto: "Hedgehog signaling enhances core-binding factor al and receptor activator of nuclear factor-kappaB ligand (RANKL) gene expression in chondrocytes"J.Endocrinol.. 177. 413-421 (2003)

[Publications] K.Hirata: "Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2"Bone. 32. 502-512 (2003)

[Publications] T.Komori: "Requisite roles of Runx2 and Cbfb in skeletal development"J.Bone Miner.Metab.. 21. 193-197 (2003)

[Publications] M.Iwamoto: "Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP)"Osteoarthritis Cartilage. 11. 6-15 (2003)

小守壽文大阪大学, 医学系研究科, 助手 (00252677)