Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
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<sup>-/-</sup> 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<sup>-/-</sup> 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.
Authors
- Jason D. Turner (ORCID: https://orcid.org/0000-0002-5423-5302)
- Jonathan R. C. Woods (ORCID: https://orcid.org/0000-0002-1201-4456)
- Helen M. McGettrick (ORCID: https://orcid.org/0000-0002-5950-8840)
- Victoria L. Heath
- Julia E. Manning
- Amy J. Naylor (ORCID: https://orcid.org/0000-0001-8384-8215)
- Roy Bicknell (ORCID: https://orcid.org/0000-0002-0941-8919)
- Jenefa Begum (ORCID: https://orcid.org/0000-0002-2992-0578)
- Isaac Dean (ORCID: https://orcid.org/0000-0002-4750-5335)
- Kabir A. Khan (ORCID: https://orcid.org/0000-0001-8453-3485)
- Christopher Dominic Buckley (ORCID: https://orcid.org/0000-0001-6924-6402)
- Muhammad Arham Sahu (ORCID: https://orcid.org/0000-0003-1043-1819)
- Simon W. Jones (ORCID: https://orcid.org/0000-0001-6785-2310)
- Ilaria Bellantuono (ORCID: https://orcid.org/0000-0001-9994-6987)
- Georgiana Neag (ORCID: https://orcid.org/0000-0002-3087-867X)
- Melissa Finlay (ORCID: https://orcid.org/0000-0003-1832-353X)
- Gowsihan Poologasundarampillai (ORCID: https://orcid.org/0000-0002-8498-323X)
- Jonathan J. Lewis
Institutions
- Sunnybrook Health Science Centre (CA)
- University of Toronto (CA)
- University College Birmingham (GB)
- University of Oxford (GB)
- Sunnybrook Research Institute
- University of Birmingham (GB)
- University of Sheffield (GB)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1038/s42003-024-06971-3
- Citations
- 4
- Primary Topic
- TGF-β signaling in diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- University of Oxford
- Versus Arthritis
- Medical Research Council