Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning

Commun Biol. 2024 Oct 11;7(1):1296. doi: 10.1038/s42003-024-06971-3.

Abstract

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.

MeSH terms

  • Animals
  • Cancellous Bone / metabolism
  • Endothelial Cells* / metabolism
  • Lectins, C-Type* / genetics
  • Lectins, C-Type* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoblasts* / cytology
  • Osteoblasts* / metabolism
  • Osteogenesis*

Substances

  • Lectins, C-Type