The University of Southampton
University of Southampton Institutional Repository

Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo

Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo
Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo
The mechanisms by which bone resorbing osteoclasts form and are activated by hormones are poorly understood. We show here that the generation of oxygen-derived free radicals in cultured bone is associated with the formation of new osteoclasts and enhanced bone resorption, identical to the effects seen when bones are treated with hormones such as parathyroid hormone (PTH) and interleukin 1 (IL-1). When free oxygen radicals were generated adjacent to bone surfaces in vivo, osteoclasts were also formed. PTH and IL-1-stimulated bone resorption was inhibited by both natural and recombinant superoxide dismutase, an enzyme that depletes tissues of superoxide anions. We used the marker nitroblue tetrazolium (NBT) to identify the cells that were responsible for free radical production in resorbing bones. NBT staining was detected only in osteoclasts in cultures of resorbing bones. NBT staining in osteoclasts was decreased in bones coincubated with calcitonin, an inhibitor of bone resorption. We also found that isolated avian osteoclasts stained positively for NBT. NBT staining in isolated osteoclasts was increased when the cells were incubated with bone particles, to which they attach. We confirmed the formation of superoxide anion in isolated avian osteoclasts using ferricytochrome c reduction as a method of detection. The reduction of ferricytochrome c in isolated osteoclasts was inhibited by superoxide dismutase. Our results suggest that oxygen-derived free radicals, and particularly the superoxide anion, are intermediaries in the formation and activation of osteoclasts.
0021-9738
632-639
Garrett, I.R.
c7663ed8-a87f-4731-8684-fbec532e8e58
Boyce, B.F.
4e33d53b-9692-4bee-9df9-e420c99bff0b
Oreffo, R.O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Bonewald, L.
cb11c595-a035-486c-8dc5-939dcafd63dd
Poser, J.
df8e7de0-f397-4666-b8a0-43c06ae5e661
Mundy, G.R.
921d7037-eb6c-48bb-97a0-52d2647ccfda
Garrett, I.R.
c7663ed8-a87f-4731-8684-fbec532e8e58
Boyce, B.F.
4e33d53b-9692-4bee-9df9-e420c99bff0b
Oreffo, R.O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Bonewald, L.
cb11c595-a035-486c-8dc5-939dcafd63dd
Poser, J.
df8e7de0-f397-4666-b8a0-43c06ae5e661
Mundy, G.R.
921d7037-eb6c-48bb-97a0-52d2647ccfda

Garrett, I.R., Boyce, B.F., Oreffo, R.O., Bonewald, L., Poser, J. and Mundy, G.R. (1990) Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. Journal of Clinical Investigation, 85 (3), 632-639. (doi:10.1172/JCI114485). (PMID:2312718)

Record type: Article

Abstract

The mechanisms by which bone resorbing osteoclasts form and are activated by hormones are poorly understood. We show here that the generation of oxygen-derived free radicals in cultured bone is associated with the formation of new osteoclasts and enhanced bone resorption, identical to the effects seen when bones are treated with hormones such as parathyroid hormone (PTH) and interleukin 1 (IL-1). When free oxygen radicals were generated adjacent to bone surfaces in vivo, osteoclasts were also formed. PTH and IL-1-stimulated bone resorption was inhibited by both natural and recombinant superoxide dismutase, an enzyme that depletes tissues of superoxide anions. We used the marker nitroblue tetrazolium (NBT) to identify the cells that were responsible for free radical production in resorbing bones. NBT staining was detected only in osteoclasts in cultures of resorbing bones. NBT staining in osteoclasts was decreased in bones coincubated with calcitonin, an inhibitor of bone resorption. We also found that isolated avian osteoclasts stained positively for NBT. NBT staining in isolated osteoclasts was increased when the cells were incubated with bone particles, to which they attach. We confirmed the formation of superoxide anion in isolated avian osteoclasts using ferricytochrome c reduction as a method of detection. The reduction of ferricytochrome c in isolated osteoclasts was inhibited by superoxide dismutase. Our results suggest that oxygen-derived free radicals, and particularly the superoxide anion, are intermediaries in the formation and activation of osteoclasts.

Full text not available from this repository.

More information

Published date: March 1990
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 360850
URI: https://eprints.soton.ac.uk/id/eprint/360850
ISSN: 0021-9738
PURE UUID: 1263e794-a262-40f1-b398-abbe867547a9
ORCID for R.O. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 08 Jan 2014 16:26
Last modified: 06 Jun 2018 12:53

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×