dc.contributor.author |
Grey, Andrew |
en |
dc.contributor.author |
Chaussade, CM |
en |
dc.contributor.author |
Empson, Victoria |
en |
dc.contributor.author |
Lin, Jianming |
en |
dc.contributor.author |
Watson, Maureen |
en |
dc.contributor.author |
O'Sullivan, Susannah |
en |
dc.contributor.author |
Rewcastle, Gordon |
en |
dc.contributor.author |
Naot, Dorit |
en |
dc.contributor.author |
Cornish, Jillian |
en |
dc.contributor.author |
Shepherd, Peter |
en |
dc.date.accessioned |
2012-02-26T19:20:08Z |
en |
dc.date.issued |
2010 |
en |
dc.identifier.citation |
Biochemical and Biophysical Research Communications 391(1):564-569 2010 |
en |
dc.identifier.issn |
0006-291X |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/11962 |
en |
dc.description.abstract |
Signaling through phosphatidylinositol-3 kinases (PI3K) regulates fundamental cellular processes such as survival and growth, and these lipid kinases are currently being investigated as therapeutic targets in several contexts. In skeletal tissue, experiments using pan-specific PI3K inhibitors have suggested that PI3K signaling influences both osteoclast and osteoblast function, but the contributions of specific PI3K isoforms to these effects have not been examined. In the current work, we assessed the effects of pharmacological inhibitors of the class Ia PI3Ks, a, b, and d, on bone cell growth, differentiation and function in vitro. Each of the class Ia PI3K isoforms is expressed and functionally active in bone cells. No consistent effects of inhibitors of p110-b or p110-d on bone cells were observed. Inhibitors of p110-a decreased osteoclastogenesis by 60–80% (p < 0.001 vs control) by direct actions on osteoclast precursors, and decreased the resorptive activity of mature osteoclasts by 60% (p < 0.01 vs control). The p110-a inhibitors also decreased the growth of osteoblastic and stromal cells (p < 0.001 vs control), and decreased differentiated osteoblast function by 30% (p < 0.05 vs control). These data suggest that signaling through the p110-a isoform of class Ia PI3Ks positively regulates the development and function of both osteoblasts and osteoclasts. Therapeutic agents that target this enzyme have the potential to significantly affect bone homeostasis, and evaluation of skeletal endpoints in clinical trials of such agents is warranted. |
en |
dc.publisher |
Elsevier Inc. |
en |
dc.relation.ispartofseries |
Biochemical and Biophysical Research Communications |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0006-291X/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Evidence for a role of the p110-alpha isoform of P13K in skeletal function |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bbrc.2009.11.099 |
en |
pubs.issue |
1 |
en |
pubs.begin-page |
564 |
en |
pubs.volume |
391 |
en |
dc.rights.holder |
Copyright: Elsevier Inc. |
en |
dc.identifier.pmid |
19931507 |
en |
pubs.end-page |
569 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
98239 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
School of Medicine |
en |
pubs.org-id |
Medicine Department |
en |
pubs.org-id |
Ophthalmology Department |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
19931507 |
en |