1999 Fiscal Year Annual Research Report

軟骨、骨の発生と再生における副甲状腺ホルモンとその関連蛋白の役割

Research Project

Project/Area Number	10044293
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	Hiroshima University
Principal Investigator	加藤幸夫広島大学, 歯学部, 教授 (10112062)
Co-Investigator(Kenkyū-buntansha)	申鳴広島大学, 歯学部, 教務員 (20294572) 中舛和子広島大学, 歯学部, 助手 (00311811) 能城光秀広島大学, 歯学部, 助教授 (00144858)
Keywords	副甲状腺ホルモン / 副甲状腺ホルモン様ペプチド / 軟骨細胞 / レチノール結合タンパク / ノックアウトマウス
Research Abstract	ウサギ初代軟骨細胞培養系に各種の成長因子を添加してIndian hedgehog(Ihh)のmRNA発現に及ぼす影響を検討した。数回の実験で、PTHとPTHrPのみが顕著にIhhの発現を抑制して、BMPとレチノイン酸は強力に促進した(骨代謝学会発表1999)。本研究ではPTHとレチノイン酸の作用をさらに詳細に検討した。PTH/PTHrPの作用は環状AMPの上昇により仲介されていることが判明した。また蛋白合成阻害剤存在下でもPTHとPTHrPはIhhの発現を抑制した。一方、レチノイン酸のIhh発現促進作用は蛋白合成阻害剤により完全に阻止された。またRNA合成阻害剤であるactinomycinD存在下で、PTHとPTHrPはIhh mRNAの半減期に影響しなかった。すなわち、PTHとPTHrPはIhh遺伝子発現を直接抑制することが示唆された。軟骨細胞培養系にRBPを添加すると、PTHの添加と同様に、レチノイン酸の軟骨分化抑制効果を部分的ではあるが、減少させた。また新規RhoGEFであるCDEP mRNAの発現を、PTHと環状AMPは一時間以内に促進した。さらに未分化間葉系細胞へPTHで誘導されるDEC1遺伝子(転写因子)を過剰発現させたところ軟骨への分化が誘導された。以上の結果は、PTHによる軟骨分化の制御機構に、Ihh、CDEP、DEC1などの新規シグナル分子が関与していることを示している。

Research Products

(8 results)

All Other

All Publications (8 results)

[Publications] Kawashima-Ohya,Y.,et al.: "Retinol-binding protein is produced by rabbit chondrocytes and responds to parathyroid hormone(PTH)/PTH-related peptide-cyclic adenosine monophosphate pathway."Endocrinology. 140. 1075-1081 (1999)
[Publications] Makihira,S.,et al.: "Enhancement of cell adhesion and spreading by a cartilage-speciffic noncollagenous protein,cartilage matrix protein (CMP/Matrilin-1),via integrin α1β1."J.Biol.Chem.. 274. 11417-11423 (1999)
[Publications] Fujimoto,E.,et al.: "Beneficial effect of basic fibroblast growth factor on the repair of full-thickness defects in rabbit articular cartilage."Arch.Orthop.Trauma Surg.. 119. 139-145 (1999)
[Publications] Ohno,S.,et al.: "RGD CAP(βig-h3)enhances the spreading of chondrocytes and fibroblasts via integrin α1β1."Biochimica et Biophysica Acta. 1451. 196-205 (1999)
[Publications] Nakamasu K.,et al.: "Membrane-bound transferrin-like protein(MTf): structure,evolution and selective expression during chondrogenetic differentiation of mouse embryonic cells."Biochimica et Biophysica Acta,. 1447. 258-264 (1999)
[Publications] Shimazu,A.,et al.: "Expression of syndecan-2,-4,and fibroblast growth factor receptor type I in human periodontal ligament fibroblasts and down-regulation of these membrane proteins during differentiation."Journal of Dental Research. 78. 1791-1799 (1999)
[Publications] Brady-KP,et al.: "A novel putative transporter maps to the osteosclerosis (oc) mutation and is not expressed in the oc mutant mouse."Genomics. 56. 254-261 (1999)
[Publications] Levy-JI,et al.: "Determinants of nitrogen dioxide concentrations in indoor ice skating rinks."Am-J-Public-Health.. 88. 1781-1786 (1998)

1999 Fiscal Year Annual Research Report

軟骨、骨の発生と再生における副甲状腺ホルモンとその関連蛋白の役割

Principal Investigator

加藤 幸夫 広島大学, 歯学部, 教授 (10112062)

Research Products

[Publications] Kawashima-Ohya,Y.,et al.: "Retinol-binding protein is produced by rabbit chondrocytes and responds to parathyroid hormone(PTH)/PTH-related peptide-cyclic adenosine monophosphate pathway."Endocrinology. 140. 1075-1081 (1999)

[Publications] Makihira,S.,et al.: "Enhancement of cell adhesion and spreading by a cartilage-speciffic noncollagenous protein,cartilage matrix protein (CMP/Matrilin-1),via integrin α1β1."J.Biol.Chem.. 274. 11417-11423 (1999)

[Publications] Fujimoto,E.,et al.: "Beneficial effect of basic fibroblast growth factor on the repair of full-thickness defects in rabbit articular cartilage."Arch.Orthop.Trauma Surg.. 119. 139-145 (1999)

[Publications] Ohno,S.,et al.: "RGD CAP(βig-h3)enhances the spreading of chondrocytes and fibroblasts via integrin α1β1."Biochimica et Biophysica Acta. 1451. 196-205 (1999)

[Publications] Nakamasu K.,et al.: "Membrane-bound transferrin-like protein(MTf): structure,evolution and selective expression during chondrogenetic differentiation of mouse embryonic cells."Biochimica et Biophysica Acta,. 1447. 258-264 (1999)

[Publications] Shimazu,A.,et al.: "Expression of syndecan-2,-4,and fibroblast growth factor receptor type I in human periodontal ligament fibroblasts and down-regulation of these membrane proteins during differentiation."Journal of Dental Research. 78. 1791-1799 (1999)

[Publications] Brady-KP,et al.: "A novel putative transporter maps to the osteosclerosis (oc) mutation and is not expressed in the oc mutant mouse."Genomics. 56. 254-261 (1999)

[Publications] Levy-JI,et al.: "Determinants of nitrogen dioxide concentrations in indoor ice skating rinks."Am-J-Public-Health.. 88. 1781-1786 (1998)

加藤幸夫広島大学, 歯学部, 教授 (10112062)