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 o...

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Asıl Yazarlar: 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
Materyal Türü: Journal article
Dil:English
Baskı/Yayın Bilgisi: Nature Research 2024
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author 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
author_facet 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
author_sort Neag, G
collection OXFORD
description 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.
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spelling oxford-uuid:4c241b81-7805-40bd-a01b-e63cc1218d092024-10-11T20:08:20ZType-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterningJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4c241b81-7805-40bd-a01b-e63cc1218d09EnglishJisc Publications RouterNature Research2024Neag, GLewis, JTurner, JDManning, JEDean, IFinlay, MPoologasundarampillai, GWoods, JSahu, MAKhan, KABegum, JMcGettrick, HMBellantuono, IHeath, VJones, SWBuckley, CDBicknell, RNaylor, AJType-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.
spellingShingle 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 endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
title Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
title_full Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
title_fullStr Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
title_full_unstemmed Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
title_short Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
title_sort type h endothelial cell protein clec14a orchestrates osteoblast activity during trabecular bone formation and patterning
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