Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity

Abstract Vitronectin (VN) is a glycoprotein found in extracellular matrix and blood. Collagen, a major extracellular matrix component in mammals, is degraded by cathepsin K (CatK), which is essential for bone resorption under acidic conditions. The relationship between VN and cathepsins has been unc...

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Autores principales:	Kimie Date, Hiromi Sakagami, Kei Yura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9d05c6eb7f74908a19bfe686df18e63
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spelling	oai:doaj.org-article:a9d05c6eb7f74908a19bfe686df18e632021-12-02T17:48:00ZRegulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity10.1038/s41598-021-91353-62045-2322https://doaj.org/article/a9d05c6eb7f74908a19bfe686df18e632021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91353-6https://doaj.org/toc/2045-2322Abstract Vitronectin (VN) is a glycoprotein found in extracellular matrix and blood. Collagen, a major extracellular matrix component in mammals, is degraded by cathepsin K (CatK), which is essential for bone resorption under acidic conditions. The relationship between VN and cathepsins has been unclear. We discovered that VN promoted collagen fibril formation and inhibited CatK activity, and observed its activation in vitro. VN accelerated collagen fibril formation at neutral pH. Collagen fibers formed with VN were in close contact with each other and appeared as scattered flat masses in scanning electron microscopy images. VN formed collagen fibers with high acid solubility and significantly inhibited CatK; the IC50 was 8.1–16.6 nM and competitive, almost the same as those of human and porcine VNs. VN inhibited the autoprocessing of inactive pro-CatK from active CatK. DeN-glycosylation of VN attenuated the inhibitory effects of CatK and its autoprocessing by VN, but had little effect on acid solubilization of collagen and VN degradation via CatK. CatK inhibition is an attractive treatment approach for osteoporosis and osteoarthritis. These findings suggest that glycosylated VN is a potential biological candidate for CatK inhibition and may help to understand the molecular mechanisms of tissue re-modeling.Kimie DateHiromi SakagamiKei YuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kimie Date Hiromi Sakagami Kei Yura Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
description	Abstract Vitronectin (VN) is a glycoprotein found in extracellular matrix and blood. Collagen, a major extracellular matrix component in mammals, is degraded by cathepsin K (CatK), which is essential for bone resorption under acidic conditions. The relationship between VN and cathepsins has been unclear. We discovered that VN promoted collagen fibril formation and inhibited CatK activity, and observed its activation in vitro. VN accelerated collagen fibril formation at neutral pH. Collagen fibers formed with VN were in close contact with each other and appeared as scattered flat masses in scanning electron microscopy images. VN formed collagen fibers with high acid solubility and significantly inhibited CatK; the IC50 was 8.1–16.6 nM and competitive, almost the same as those of human and porcine VNs. VN inhibited the autoprocessing of inactive pro-CatK from active CatK. DeN-glycosylation of VN attenuated the inhibitory effects of CatK and its autoprocessing by VN, but had little effect on acid solubilization of collagen and VN degradation via CatK. CatK inhibition is an attractive treatment approach for osteoporosis and osteoarthritis. These findings suggest that glycosylated VN is a potential biological candidate for CatK inhibition and may help to understand the molecular mechanisms of tissue re-modeling.
format	article
author	Kimie Date Hiromi Sakagami Kei Yura
author_facet	Kimie Date Hiromi Sakagami Kei Yura
author_sort	Kimie Date
title	Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
title_short	Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
title_full	Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
title_fullStr	Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
title_full_unstemmed	Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity
title_sort	regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin k activity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a9d05c6eb7f74908a19bfe686df18e63
work_keys_str_mv	AT kimiedate regulatorypropertiesofvitronectinanditsglycosylationincollagenfibrilformationandcollagendegradingenzymecathepsinkactivity AT hiromisakagami regulatorypropertiesofvitronectinanditsglycosylationincollagenfibrilformationandcollagendegradingenzymecathepsinkactivity AT keiyura regulatorypropertiesofvitronectinanditsglycosylationincollagenfibrilformationandcollagendegradingenzymecathepsinkactivity
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Regulatory properties of vitronectin and its glycosylation in collagen fibril formation and collagen-degrading enzyme cathepsin K activity

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