P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis

Abstract Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ning Wang, Ankita Agrawal, Niklas Rye Jørgensen, Alison Gartland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/593ec7c4879b49588c24789f6eff118a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:593ec7c4879b49588c24789f6eff118a
record_format	dspace
spelling	oai:doaj.org-article:593ec7c4879b49588c24789f6eff118a2021-12-02T12:32:35ZP2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis10.1038/s41598-018-21574-92045-2322https://doaj.org/article/593ec7c4879b49588c24789f6eff118a2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21574-9https://doaj.org/toc/2045-2322Abstract Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of bone loss and vertebral fractures in post-menopausal women. In this study we use a mouse model of oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R−/− to show that absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were isolated from both BALB/cJ P2X7R−/− and BALB/cJ P2X7R+/+ mice and then cultured in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R−/− derived precursors generated slightly more osteoclasts but with a significant reduction in the amount of resorption per osteoclast. Furthermore, when using modified culture conditions osteoclast activity was additionally increased in the absence of the P2X7R suggest that P2X7R may regulate the lifespan and activity of osteoclasts. Finally using mechanical loading as an anabolic stimulus for bone formation, we demonstrated that the increased oestrogen-deficient bone loss could be rescued, even in the absence of P2X7R. This study paves the way for clinical intervention for women with post-menopausal osteoporosis and P2XR7 loss of function polymorphisms.Ning WangAnkita AgrawalNiklas Rye JørgensenAlison GartlandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ning Wang Ankita Agrawal Niklas Rye Jørgensen Alison Gartland P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
description	Abstract Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of bone loss and vertebral fractures in post-menopausal women. In this study we use a mouse model of oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R−/− to show that absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were isolated from both BALB/cJ P2X7R−/− and BALB/cJ P2X7R+/+ mice and then cultured in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R−/− derived precursors generated slightly more osteoclasts but with a significant reduction in the amount of resorption per osteoclast. Furthermore, when using modified culture conditions osteoclast activity was additionally increased in the absence of the P2X7R suggest that P2X7R may regulate the lifespan and activity of osteoclasts. Finally using mechanical loading as an anabolic stimulus for bone formation, we demonstrated that the increased oestrogen-deficient bone loss could be rescued, even in the absence of P2X7R. This study paves the way for clinical intervention for women with post-menopausal osteoporosis and P2XR7 loss of function polymorphisms.
format	article
author	Ning Wang Ankita Agrawal Niklas Rye Jørgensen Alison Gartland
author_facet	Ning Wang Ankita Agrawal Niklas Rye Jørgensen Alison Gartland
author_sort	Ning Wang
title	P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
title_short	P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
title_full	P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
title_fullStr	P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
title_full_unstemmed	P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
title_sort	p2x7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/593ec7c4879b49588c24789f6eff118a
work_keys_str_mv	AT ningwang p2x7receptorregulatesosteoclastfunctionandbonelossinamousemodelofosteoporosis AT ankitaagrawal p2x7receptorregulatesosteoclastfunctionandbonelossinamousemodelofosteoporosis AT niklasryejørgensen p2x7receptorregulatesosteoclastfunctionandbonelossinamousemodelofosteoporosis AT alisongartland p2x7receptorregulatesosteoclastfunctionandbonelossinamousemodelofosteoporosis
_version_	1718394036208795648

P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis

Ejemplares similares