Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.

The formation of insoluble amyloid fibrils is associated with an array of devastating human diseases. Dialysis-related amyloidosis (DRA) is a severe complication of hemodialysis that results in the progressive destruction of the bones and joints. Elevated concentrations of β(2)-microglobulin (β(2)m)...

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Autores principales:	Morwenna Y Porter, Katy E Routledge, Sheena E Radford, Eric W Hewitt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/20b7cc135f9547f29f11979bb39ba3f7
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spelling	oai:doaj.org-article:20b7cc135f9547f29f11979bb39ba3f72021-11-18T07:34:38ZCharacterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.1932-620310.1371/journal.pone.0027353https://doaj.org/article/20b7cc135f9547f29f11979bb39ba3f72011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22096558/?tool=EBIhttps://doaj.org/toc/1932-6203The formation of insoluble amyloid fibrils is associated with an array of devastating human diseases. Dialysis-related amyloidosis (DRA) is a severe complication of hemodialysis that results in the progressive destruction of the bones and joints. Elevated concentrations of β(2)-microglobulin (β(2)m) in the serum of subjects on hemodialysis promote the formation of amyloid fibrils in the osteoarticular tissues, but the cellular basis for the destruction of these tissues in DRA is poorly understood. In this study we performed a systematic analysis of the interaction of monomeric and fibrillar β(2)m with primary human cells of the types present in the synovial joints of subjects with DRA. Building upon observations that macrophages infiltrate β(2)m amyloid deposits in vivo we demonstrate that monocytes, the precursors of macrophages, cannot degrade β(2)m fibrils, and that both monomeric β(2)m and fibrillar β(2)m are cytotoxic to these cells. β(2)m fibrils also impair the formation of bone resorbing osteoclasts from monocytes and reduce the viability of osteoblasts, the cell type that produces bone. As a consequence, we predict that β(2)m amyloid will disrupt the remodelling of the bone, which is critical for the maintenance of this tissue. Moreover, we show that β(2)m fibrils reduce the viability of chondrocytes, rationalizing the loss of cartilage in DRA. Together, our observations demonstrate that β(2)m cytotoxicity has multiple cellular targets in the osteoarticular tissues and is likely to be a key factor in the bone and joint destruction characteristic of DRA.Morwenna Y PorterKaty E RoutledgeSheena E RadfordEric W HewittPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27353 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Morwenna Y Porter Katy E Routledge Sheena E Radford Eric W Hewitt Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
description	The formation of insoluble amyloid fibrils is associated with an array of devastating human diseases. Dialysis-related amyloidosis (DRA) is a severe complication of hemodialysis that results in the progressive destruction of the bones and joints. Elevated concentrations of β(2)-microglobulin (β(2)m) in the serum of subjects on hemodialysis promote the formation of amyloid fibrils in the osteoarticular tissues, but the cellular basis for the destruction of these tissues in DRA is poorly understood. In this study we performed a systematic analysis of the interaction of monomeric and fibrillar β(2)m with primary human cells of the types present in the synovial joints of subjects with DRA. Building upon observations that macrophages infiltrate β(2)m amyloid deposits in vivo we demonstrate that monocytes, the precursors of macrophages, cannot degrade β(2)m fibrils, and that both monomeric β(2)m and fibrillar β(2)m are cytotoxic to these cells. β(2)m fibrils also impair the formation of bone resorbing osteoclasts from monocytes and reduce the viability of osteoblasts, the cell type that produces bone. As a consequence, we predict that β(2)m amyloid will disrupt the remodelling of the bone, which is critical for the maintenance of this tissue. Moreover, we show that β(2)m fibrils reduce the viability of chondrocytes, rationalizing the loss of cartilage in DRA. Together, our observations demonstrate that β(2)m cytotoxicity has multiple cellular targets in the osteoarticular tissues and is likely to be a key factor in the bone and joint destruction characteristic of DRA.
format	article
author	Morwenna Y Porter Katy E Routledge Sheena E Radford Eric W Hewitt
author_facet	Morwenna Y Porter Katy E Routledge Sheena E Radford Eric W Hewitt
author_sort	Morwenna Y Porter
title	Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
title_short	Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
title_full	Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
title_fullStr	Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
title_full_unstemmed	Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
title_sort	characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/20b7cc135f9547f29f11979bb39ba3f7
work_keys_str_mv	AT morwennayporter characterizationoftheresponseofprimarycellsrelevanttodialysisrelatedamyloidosistob2microglobulinmonomerandfibrils AT katyeroutledge characterizationoftheresponseofprimarycellsrelevanttodialysisrelatedamyloidosistob2microglobulinmonomerandfibrils AT sheenaeradford characterizationoftheresponseofprimarycellsrelevanttodialysisrelatedamyloidosistob2microglobulinmonomerandfibrils AT ericwhewitt characterizationoftheresponseofprimarycellsrelevanttodialysisrelatedamyloidosistob2microglobulinmonomerandfibrils
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Characterization of the response of primary cells relevant to dialysis-related amyloidosis to β2-microglobulin monomer and fibrils.

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