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

Georgiana Neag; Jonny Lewis; Jason Turner; Julia Manning; Isaac Dean; Melissa Finlay; Gowsihan Poologasundarampillai; Jonathan Woods; Muhammad Arham Sahu; Kabir A Khan; Jenefa Begum; Helen McGettrick; Ilaria Bellantuono; Victoria Heath; Simon Jones; Christopher Buckley; Roy Bicknell; Amy Naylor

doi:10.1038/s42003-024-06971-3

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

Georgiana Neag, Jonny Lewis, Jason Turner, Julia Manning, Isaac Dean, Melissa Finlay, Gowsihan Poologasundarampillai, Jonathan Woods, Muhammad Arham Sahu, Kabir A Khan, Jenefa Begum, Helen McGettrick, Ilaria Bellantuono, Victoria Heath, Simon Jones, Christopher Buckley, Roy Bicknell, Amy Naylor^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	1296
Number of pages	13
Journal	Communications Biology
Volume	7
DOIs	https://doi.org/10.1038/s42003-024-06971-3
Publication status	Published - 11 Oct 2024

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10.1038/s42003-024-06971-3Licence: Creative Commons: Attribution (CC BY)

NeagG2024Type-HFinal published version, 8.24 MBLicence: Creative Commons: Attribution (CC BY)

Type 14 C-type lectins link endothelial cells and bone remodelling in inflammatory arthiritis
Naylor, A. (Principal Investigator)
ARTHRITIS RESEARCH UK
1/01/18 → 31/12/24
Project: Research
MRC - ARUK Centre for Musculoskeletal Ageing Research
Jones, S. (Co-Investigator), Buckley, C. (Co-Investigator), Lord, J. (Principal Investigator), Greig, C. (Co-Investigator) & Raza, K. (Co-Investigator)
Medical Research Council
1/10/17 → 30/06/23
Project: Research Councils

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Neag, G., Lewis, J., Turner, J., Manning, J., Dean, I., Finlay, M., Poologasundarampillai, G., Woods, J., Arham Sahu, M., Khan, K. A., Begum, J., McGettrick, H., Bellantuono, I., Heath, V., Jones, S., Buckley, C., Bicknell, R., & Naylor, A. (2024). Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning. Communications Biology, 7, Article 1296. https://doi.org/10.1038/s42003-024-06971-3

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

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 novelmechanism that mediates this vital cellular crosstalk.",

author = "Georgiana Neag and Jonny Lewis and Jason Turner and Julia Manning and Isaac Dean and Melissa Finlay and Gowsihan Poologasundarampillai and Jonathan Woods and \{Arham Sahu\}, Muhammad and Khan, \{Kabir A\} and Jenefa Begum and Helen McGettrick and Ilaria Bellantuono and Victoria Heath and Simon Jones and Christopher Buckley and Roy Bicknell and Amy Naylor",

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doi = "10.1038/s42003-024-06971-3",

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Neag, G, Lewis, J, Turner, J, Manning, J, Dean, I, Finlay, M, Poologasundarampillai, G, Woods, J, Arham Sahu, M, Khan, KA, Begum, J , McGettrick, H, Bellantuono, I, Heath, V , Jones, S, Buckley, C, Bicknell, R & Naylor, A 2024, 'Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning', Communications Biology, vol. 7, 1296. https://doi.org/10.1038/s42003-024-06971-3

TY - JOUR

T1 - Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning

AU - Neag, Georgiana

AU - Lewis, Jonny

AU - Turner, Jason

AU - Manning, Julia

AU - Dean, Isaac

AU - Finlay, Melissa

AU - Poologasundarampillai, Gowsihan

AU - Woods, Jonathan

AU - Arham Sahu, Muhammad

AU - Khan, Kabir A

AU - Begum, Jenefa

AU - McGettrick, Helen

AU - Bellantuono, Ilaria

AU - Heath, Victoria

AU - Jones, Simon

AU - Buckley, Christopher

AU - Bicknell, Roy

AU - Naylor, Amy

PY - 2024/10/11

Y1 - 2024/10/11

N2 - 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 novelmechanism that mediates this vital cellular crosstalk.

AB - 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 novelmechanism that mediates this vital cellular crosstalk.

U2 - 10.1038/s42003-024-06971-3

DO - 10.1038/s42003-024-06971-3

M3 - Article

SN - 2399-3642

VL - 7

JO - Communications Biology

JF - Communications Biology

M1 - 1296

ER -

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

Abstract

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Type 14 C-type lectins link endothelial cells and bone remodelling in inflammatory arthiritis

MRC - ARUK Centre for Musculoskeletal Ageing Research

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