骨形成細胞(骨芽細胞)が分泌する未知タンパクの同定とその骨疾患での意義

1998 年度 実績報告書

• 研究課題/領域番号: 07407040
• 研究機関: 信州大学
• 研究代表者: 高岡 邦夫 信州大学, 医学部整形外科学, 教授 (30112048)
• 研究分担者: 大久保 公策 大阪大学, 細胞工学センター, 助教授 (40233069) ; 吉村 康夫 信州大学, 医学部附属病院整形外科, 助手 (10303439) ; 清水 富永 信州大学, 医学部整形外科学, 助手 (40283270)
• キーワード: 骨芽細胞 / 骨基質タンパク / 遺伝子

研究概要

骨形成機構の更なる理解と骨粗鬆症に代表される骨代謝疾患の病態解明のため、骨芽細胞の発現遺伝子の分析を通じて、骨芽細胞の新規機能の解明を行ってきた。その結果、ヒト骨芽細胞に発現している6個の新規遺伝子(Osteohlast specific gene;OBS1〜6)の全長を決定した。OBS1は全長2075bp、509アミノ酸残基からなり、insulin like glowth factor binding proteinとhomologyが高い。OBS2は、3127bp、846アミノ酸残基でCarboxypeptids Nと高いhomologyを持つ。OBS3は、4847bp、1382アミノ酸をcodeし基底膜に存在する基質蛋白であるnidogenと塩基配列で55%、翻訳したアミノ酸配列で38%のidentityを認める骨基質蛋白であり重要なmotif構造を持ち、nidogenの相同性より骨基質においてcollagenと他の基質蛋白質の橋渡し役をするものと考えられる。OBS4は、2475bp、232アミノ酸からなる。OBS5は、1513bp、408アミノ酸残基からなり、C.elegansのgenome上のhypothetical proteinとHomologyが高い。OBS6は全長3016bp、845アミノ酸残基からなりマウスAEBP1(adipoyte enhancer binding site binding protein 1)のヒトに対応する遺伝子である。AEBP1は、脂肪細胞の分化の研究で発見された遺伝子で、脂肪細胞の分化とともに発現が抑制され、脂肪細胞特異的遺伝子の発現抑制機能を持つことから、脂肪細胞の分化抑制能を持つと考えられている。この遺伝子が、脂肪細胞と起源を同じくする骨芽細胞にも発現しており、脂肪細胞と同様に骨芽細胞の分化とともに抑制されることから骨芽細胞においても分化抑制能を持つものと考えられる。また、実際の骨形成の場でのAEBP1の発現をin situ hyhridizationでみてみると仮骨を旺盛に形成している骨芽細胞に強い発現を認めた。他に非常にシステインに富む骨基質蛋白、甲状腺ホルモンに対する新規レセプターやまったく未知の遺伝子が同定されている。さらに新規遺伝子の同定を進めていくと同時に、その機能解析を行っている。

研究成果

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