Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.

Previous studies have shown that exogenous ATP (>1 µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the minera...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Isabel R Orriss, Michelle L Key, Mark O R Hajjawi, Timothy R Arnett
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/777578988f9745a3954f8f5e6e2a260d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:777578988f9745a3954f8f5e6e2a260d
record_format	dspace
spelling	oai:doaj.org-article:777578988f9745a3954f8f5e6e2a260d2021-11-18T07:38:03ZExtracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.1932-620310.1371/journal.pone.0069057https://doaj.org/article/777578988f9745a3954f8f5e6e2a260d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874866/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Previous studies have shown that exogenous ATP (>1 µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PP(i)). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5 U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2 P(i)). Addition of 0.5 U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5 U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PP(i)-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation.Isabel R OrrissMichelle L KeyMark O R HajjawiTimothy R ArnettPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69057 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabel R Orriss Michelle L Key Mark O R Hajjawi Timothy R Arnett Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.
description	Previous studies have shown that exogenous ATP (>1 µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PP(i)). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5 U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2 P(i)). Addition of 0.5 U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5 U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PP(i)-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation.
format	article
author	Isabel R Orriss Michelle L Key Mark O R Hajjawi Timothy R Arnett
author_facet	Isabel R Orriss Michelle L Key Mark O R Hajjawi Timothy R Arnett
author_sort	Isabel R Orriss
title	Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.
title_short	Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.
title_full	Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.
title_fullStr	Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.
title_full_unstemmed	Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.
title_sort	extracellular atp released by osteoblasts is a key local inhibitor of bone mineralisation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/777578988f9745a3954f8f5e6e2a260d
work_keys_str_mv	AT isabelrorriss extracellularatpreleasedbyosteoblastsisakeylocalinhibitorofbonemineralisation AT michellelkey extracellularatpreleasedbyosteoblastsisakeylocalinhibitorofbonemineralisation AT markorhajjawi extracellularatpreleasedbyosteoblastsisakeylocalinhibitorofbonemineralisation AT timothyrarnett extracellularatpreleasedbyosteoblastsisakeylocalinhibitorofbonemineralisation
_version_	1718423169029636096

Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.

Ejemplares similares