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Nat Cell Biol. 2019 Apr;21(4):430-441. doi: 10.1038/s41556-019-0304-7. Epub 2019 Apr 1.

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

Author information

1
Institute of Clinical Sciences, Imperial College London, London, UK.
2
MRC London Institute of Medical Sciences, Imperial College London, London, UK.
3
The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
4
Institute of Clinical Sciences, Imperial College London, London, UK. s.ramasamy@imperial.ac.uk.
5
MRC London Institute of Medical Sciences, Imperial College London, London, UK. s.ramasamy@imperial.ac.uk.

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.

PMID:
30936475
DOI:
10.1038/s41556-019-0304-7
[Indexed for MEDLINE]

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