オステオプロテゲリン:骨密度の調節に関与する新しい分泌タンパク質
W S Simonet1, D L Lacey, C R Dunstan
1Department of Molecular Genetics, Amgen Inc., Thousand Oaks, California 91320, USA.
Cell
|April 18, 1997
まとめ
新しく発見されたタンパク質であるオステオプロテゲリン (OPG) は,骨細胞の分化を阻害することによって,骨の再吸収を調節する. この発見は,OPGがOPGであることを示唆しています.
科学分野:
- 内分泌学と骨生物学について
- 分子および細胞生物学
- 受容体生物学 受容体生物学
背景:
- 骨の再吸収は,骨格細胞によって調節される重要なプロセスです.
- 骨の再吸収の調節不良は,骨粗鬆症のような疾患に寄与する.
- 骨の再吸収を調節する新しい分泌型グリコタンパク質が特定されました.
研究 の 目的:
- 骨の再吸収に関与する新しい分泌されたグリコタンパク質を特定し,特徴づけること.
- オステオクラストの分化と骨質の調節におけるこのタンパク質の役割を調査する.
- 骨粗鬆症に対するこのタンパク質の治療の可能性を調査する.
主な方法:
- 新たに分泌されるグリコタンパク質,オステオプロテゲリン (OPG) の識別と特徴付け.
- 肝臓OPG発現のトランスジェニックマウスを用いたin vivo研究.
- 再結合OPGを正常なマウスと卵巣切除されたラットに投与した.
- オステオクラストが前体細胞からの分化に及ぼす効果を評価する in vitro 研究.
主要な成果:
- トランスジェニックマウスにおける肝臓OPG発現は,骨粗鬆症と骨格細胞の分化低下につながった.
- 再結合OPGの投与は,これらの効果を正常なマウスで再現した.
- リコンビナンスのOPGは,投与量に依存して,骨格細胞の分化をin vitroで阻害しました.
- OPG投与は,ネズミの卵巣切除に伴う骨の損失を予防しました.
結論:
- オステオプロテゲリン (OPG) は,骨質を調節する溶解性因子として作用します.
- OPGはオステオクラストの分化と活動を阻害する.
- OPGは,骨粗鬆症や他の骨疾患の治療に治療的可能性を示しています.
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