Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/70947
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dc.contributor.author | Wijenayaka, A. | - |
dc.contributor.author | Kogawa, M. | - |
dc.contributor.author | Lim, H. | - |
dc.contributor.author | Bonewald, L. | - |
dc.contributor.author | Findlay, D. | - |
dc.contributor.author | Atkins, G. | - |
dc.contributor.editor | Carvalho, D.P.D. | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | PLoS One, 2011; 6(10):e25900-1-e25900-9 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2440/70947 | - |
dc.description | Extent: 9p. | - |
dc.description.abstract | Sclerostin is a product of mature osteocytes embedded in mineralised bone and is a negative regulator of bone mass and osteoblast differentiation. While evidence suggests that sclerostin has an anti-anabolic role, the possibility also exists that sclerostin has catabolic activity. To test this we treated human primary pre-osteocyte cultures, cells we have found are exquisitely sensitive to sclerostin, or mouse osteocyte-like MLO-Y4 cells, with recombinant human sclerostin (rhSCL) and measured effects on pro-catabolic gene expression. Sclerostin dose-dependently up-regulated the expression of receptor activator of nuclear factor kappa B (RANKL) mRNA and down-regulated that of osteoprotegerin (OPG) mRNA, causing an increase in the RANKL:OPG mRNA ratio. To examine the effects of rhSCL on resulting osteoclastic activity, MLO-Y4 cells plated onto a bone-like substrate were primed with rhSCL for 3 days and then either mouse splenocytes or human peripheral blood mononuclear cells (PBMC) were added. This resulted in cultures with elevated osteoclastic resorption (approximately 7-fold) compared to untreated co-cultures. The increased resorption was abolished by co-addition of recombinant OPG. In co-cultures of MLO-Y4 cells with PBMC, SCL also increased the number and size of the TRAP-positive multinucleated cells formed. Importantly, rhSCL had no effect on TRAP-positive cell formation from monocultures of either splenocytes or PBMC. Further, rhSCL did not induce apoptosis of MLO-Y4 cells, as determined by caspase activity assays, demonstrating that the osteoclastic response was not driven by dying osteocytes. Together, these results suggest that sclerostin may have a catabolic action through promotion of osteoclast formation and activity by osteocytes, in a RANKL-dependent manner. | - |
dc.description.statementofresponsibility | Asiri R. Wijenayaka, Masakazu Kogawa, Hui Peng Lim, Lynda F. Bonewald, David M. Findlay and Gerald J. Atkins | - |
dc.language.iso | en | - |
dc.publisher | Public Library of Science | - |
dc.rights | Copyright: © 2011 Wijenayaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | - |
dc.source.uri | http://dx.doi.org/10.1371/journal.pone.0025900 | - |
dc.subject | Cells, Cultured | - |
dc.subject | Osteoclasts | - |
dc.subject | Osteoblasts | - |
dc.subject | Osteocytes | - |
dc.subject | Animals | - |
dc.subject | Humans | - |
dc.subject | Mice | - |
dc.subject | Acid Phosphatase | - |
dc.subject | Isoenzymes | - |
dc.subject | Adaptor Proteins, Signal Transducing | - |
dc.subject | Bone Morphogenetic Proteins | - |
dc.subject | Recombinant Proteins | - |
dc.subject | Genetic Markers | - |
dc.subject | Signal Transduction | - |
dc.subject | Apoptosis | - |
dc.subject | Cell Differentiation | - |
dc.subject | Cell Survival | - |
dc.subject | Gene Expression Regulation | - |
dc.subject | Calcification, Physiologic | - |
dc.subject | Osteogenesis | - |
dc.subject | Adult | - |
dc.subject | RANK Ligand | - |
dc.subject | Tartrate-Resistant Acid Phosphatase | - |
dc.title | Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1371/journal.pone.0025900 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Atkins, G. [0000-0002-3123-9861] | - |
Appears in Collections: | Aurora harvest Orthopaedics and Trauma publications |
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hdl_70947.pdf | Published version | 874.77 kB | Adobe PDF | View/Open |
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