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Endothelial proteolytic activity and interaction with non-resorbing osteoclasts mediate bone elongation

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Title: Endothelial proteolytic activity and interaction with non-resorbing osteoclasts mediate bone elongation
Authors: Romeo, SG
Alawi, KM
Rodrigues, J
Singh, A
Kusumbe, AP
Ramasamy, SK
Item Type: Journal Article
Abstract: Growth plate cartilage contributes to the generation of a large variety of shapes and sizes of skeletal elements in the mammalian system. The removal of cartilage and how this process regulates bone shape are not well understood. Here we identify a non-bone-resorbing osteoclast subtype termed vessel-associated osteoclast (VAO). Endothelial cells at the bone/cartilage interface support VAOs through a RANKL–RANK signalling mechanism. In contrast to classical bone-associated osteoclasts, VAOs are dispensable for cartilage resorption and regulate anastomoses of type H vessels. Remarkably, proteinases including matrix metalloproteinase-9 (Mmp9) released from endothelial cells, not osteoclasts, are essential for resorbing cartilage to lead directional bone growth. Importantly, disrupting the orientation of angiogenic blood vessels by misdirecting them results in contorted bone shape. This study identifies proteolytic functions of endothelial cells in cartilage and provides a framework to explore tissue-lytic features of blood vessels in fracture healing, arthritis and cancer.
Issue Date: 1-Apr-2019
Date of Acceptance: 26-Feb-2019
URI: http://hdl.handle.net/10044/1/69816
DOI: https://dx.doi.org/10.1038/s41556-019-0304-7
ISSN: 1465-7392
Publisher: Nature Research
Start Page: 430
End Page: 441
Journal / Book Title: Nature Cell Biology
Volume: 21
Issue: 4
Copyright Statement: © 2019 The Author(s), under exclusive licence to Springer Nature Limited. The final publication is available Springer Nature via https://dx.doi.org/10.1038/s41556-019-0304-7
Sponsor/Funder: Medical Research Council (MRC)
Wellcome Trust
Funder's Grant Number: PO#4050724483
202300/Z/16/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
ENDOCHONDRAL OSSIFICATION
DIFFERENTIAL GROWTH
INDUCED ARTHRITIS
FRACTURE REPAIR
ANGIOGENESIS
CARTILAGE
OSTEOGENESIS
CELL
APOPTOSIS
LIGAND
Animals
Bone Resorption
Bone and Bones
Cartilage
Endothelium
Growth Plate
Mice, Inbred C57BL
Osteoclasts
Osteogenesis
Peptide Hydrolases
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2019-04-01
Appears in Collections:Clinical Sciences
Molecular Sciences



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