Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning.
Neag G., Lewis J., Turner JD., Manning JE., Dean I., Finlay M., Poologasundarampillai G., Woods J., Sahu MA., Khan KA., Begum J., McGettrick HM., Bellantuono I., Heath V., Jones SW., Buckley CD., Bicknell R., Naylor AJ.
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.