Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
School of Medical Sciences, University of Birmingham, Birmingham, UK.
Commun Biol. 2024 Oct 11;7(1):1296. doi: 10.1038/s42003-024-06971-3.
Type-H capillary endothelial cells control bone formation during embryogenesis and postnatal growth but few signalling mechanisms underpinning this influence have been characterised. Here, we identify a highly expressed type-H endothelial cell protein, Clec14a, and explore its role in coordinating osteoblast activity. Expression of Clec14a and its ligand, Mmrn2 are high in murine type-H endothelial cells but absent from osteoblasts. Clec14a mice have premature condensation of the type-H vasculature and expanded distribution of osteoblasts and bone matrix, increased long-bone length and bone density indicative of accelerated skeletal development, and enhanced osteoblast maturation. Antibody-mediated blockade of the Clec14a-Mmrn2 interaction recapitulates the Clec14a phenotype. Endothelial cell expression of Clec14a regulates osteoblast maturation and mineralisation activity during postnatal bone development in mice. This finding underscores the importance of type-H capillary control of osteoblast activity in bone formation and identifies a novel mechanism that mediates this vital cellular crosstalk.
H 型毛细血管内皮细胞在胚胎发生和出生后生长过程中控制骨形成，但目前尚未描述其影响的信号机制。在这里，我们鉴定了一种高度表达的 H 型内皮细胞蛋白 Clec14a，并探索了其在协调成骨细胞活性中的作用。在鼠 H 型内皮细胞中，Clec14a 和其配体 Mmrn2 的表达水平较高，但在成骨细胞中不存在。Clec14a 小鼠的 H 型血管过早凝聚，成骨细胞和骨基质分布扩大，长骨长度和骨密度增加，表明骨骼发育加速，成骨细胞成熟增强。Clec14a-Mmrn2 相互作用的抗体介导阻断再现了 Clec14a 表型。内皮细胞表达的 Clec14a 调节小鼠出生后骨发育过程中成骨细胞的成熟和矿化活性。这一发现强调了 H 型毛细血管控制成骨细胞活性在骨形成中的重要性，并确定了一种介导这种重要细胞串扰的新机制。
