損傷後の骨の支柱再生におけるリンパ血管

Lincoln Biswas¹, Junyu Chen², Jessica De Angelis¹

¹Tissue and Tumor Microenvironments Group, MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Medical Sciences Division, University of Oxford, Oxford OX3 9DS, UK.

Cell

|January 20, 2023

まとめ

骨リンパ管は遺伝子毒性ストレス中に発見され,CXCL12シグナル伝達によって骨と血液形成の再生を助けます. この発見は,リンパ血管新生が高齢動物の潜在的な治療法であることを示唆しています.

科学分野:

血管生物学
再生医療
骨格生物学

背景:

血管は骨と血液形成を調節するが,リンパ血管は骨には存在しないと考えられていた.
現在の理解では血管以外の骨の血管ネットワークに洞察力がないのです

研究の目的:

骨のリンパ系血管の存在と機能を調べる
骨と血液形成の再生におけるリンパ血管生成の役割を調査する.

主な方法:

マウスとヒトの骨のサンプルを高解像度で撮影する.
血管と細胞の反応を追跡するために細胞特有のマウス遺伝子を利用しました
遺伝子毒性ストレスに対する反応としてVEGF-C/VEGFR-3とIL6を含むシグナル伝達経路を分析した.

主要な成果:

マウスとヒトの骨にリンパ管があることが示されました
VEGF-C/VEGFR-3とIL6によって引き起こされる,遺伝子毒性ストレス中の骨リンパ血管の拡張を観察した.
リンパ内皮細胞からのCXCL12分泌は,血液形成と骨の再生に不可欠であると特定されました.
リンパ血管新生CXCL12は,骨細胞の拡張,分化,再生を促進する.
老いた動物のリンパ管の損傷と細胞の膨張を観察した.

結論:

リンパ管は骨に存在し,再生に重要な役割を果たします.
VEGF- C/ VEGFR-3シグナル伝達とIL6誘発のリンパ血管生成は,骨の修復の鍵となる.
CXCL12媒介のペリサイト分化は,骨と造血再生のための治療目標を提供します.
リンパ血管新生の年齢関連の低下は再生能力を損なう.

キーワード:

3Dイメージング IL6 について年老化骨ヘマトポエシス怪我をするリンパ血管新生リンパ系血管再生するストレス

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