頭蓋骨における骨形成の先駆者は血管である(Blood vessels are the pioneers of bone formation in the skull)

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2024-06-04 マックス・プランク研究所

生きた骨は機械的ストレスに適応し、瘢痕なく再生する能力を持ちます。通常の骨折治癒では血管と骨細胞が協力して新しい骨組織を形成しますが、頭蓋骨の治癒は異なります。ドイツのマックス・プランク分子生物医学研究所の研究チームは、高度なレーザーマイクロスコープを用いて、頭蓋骨の治癒と血管新生を観察しました。この過程では、骨前駆細胞が血管に伴わず、血管がまず単独で成長し、酸素と栄養を供給した後に骨細胞が移動してきて骨化を開始します。この研究は、頭蓋骨の治癒が長骨とは根本的に異なることを示しています。

<関連情報>

腓骨再生における血管新生は骨新生から切り離される Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration

M. Gabriele Bixel,Kishor K. Sivaraj,Melanie Timmen,Vishal Mohanakrishnan,Anusha Aravamudhan,Susanne Adams,Bong-Ihn Koh,Hyun-Woo Jeong,Kai Kruse,Richard Stange & Ralf H. Adams
Nature Communications  Published:04 June 2024
DOI:https://doi.org/10.1038/s41467-024-48579-5

頭蓋骨における骨形成の先駆者は血管である(Blood vessels are the pioneers of bone formation in the skull)

Abstract

Bone regeneration requires a well-orchestrated cellular and molecular response including robust vascularization and recruitment of mesenchymal and osteogenic cells. In femoral fractures, angiogenesis and osteogenesis are closely coupled during the complex healing process. Here, we show with advanced longitudinal intravital multiphoton microscopy that early vascular sprouting is not directly coupled to osteoprogenitor invasion during calvarial bone regeneration. Early osteoprogenitors emerging from the periosteum give rise to bone-forming osteoblasts at the injured calvarial bone edge. Microvessels growing inside the lesions are not associated with osteoprogenitors. Subsequently, osteogenic cells collectively invade the vascularized and perfused lesion as a multicellular layer, thereby advancing regenerative ossification. Vascular sprouting and remodeling result in dynamic blood flow alterations to accommodate the growing bone. Single cell profiling of injured calvarial bones demonstrates mesenchymal stromal cell heterogeneity comparable to femoral fractures with increase in cell types promoting bone regeneration. Expression of angiogenesis and hypoxia-related genes are slightly elevated reflecting ossification of a vascularized lesion site. Endothelial Notch and VEGF signaling alter vascular growth in calvarial bone repair without affecting the ossification progress. Our findings may have clinical implications for bone regeneration and bioengineering approaches.

生物化学工学
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