臨床整形外科46巻8号

2011年08月発行

最新基礎科学/知っておきたい

セマフォリンと骨代謝

著者： 竹ヶ原宜子¹

所属機関： ¹

ページ範囲：P.712 - P.717

■はじめに

　セマフォリン分子は，従来，神経シナプスを成立させるために機能する神経ガイダンス因子の代表的な分子として知られてきた^14,25)．近年，神経系における機能に加えて器官形成・血管新生，癌の進展への関与，また免疫応答制御作用などが示され^12,16,20,30)，セマフォリンの機能が多岐にわたることが明らかになっている(図1)．

　骨形成におけるセマフォリン分子の機能を示唆する報告はかなり以前になされていた．1996年，セマフォリン分子の中で初めて作製された遺伝子欠損マウスであるSema3A遺伝子欠損マウスの報告では，神経形成や心臓形態の異常に加えて，骨形態の異常が報告されていた¹⁾．しかしながら翌1997年，別のグループからSema3Aの遺伝子欠損マウスが報告され²⁴⁾，その神経系の表現型がcontroversialであったためにこの遺伝子欠損マウスの骨形態異常の表現型は見過ごされ，骨形成・骨代謝におけるセマフォリンの役割は不明なままであった．

　筆者らは骨および免疫系に高発現しているセマフォリン分子の主要な受容体・plexin-A1に着目し，その遺伝子欠損マウスの作製および解析からplexin-A1が樹状細胞および破骨細胞に発現し，免疫応答および骨形成に重要な機能を有することを明らかにした．本稿ではplexin-A1およびその下流のシグナル伝達分子による骨代謝制御について最近の知見も含めて概説したい．

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