umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Activation of Liver X Receptor (LXR) Inhibits Receptor Activator of Nuclear Factor {kappa}B Ligand (RANKL)-induced Osteoclast Differentiation in an LXR{beta}-dependent Mechanism.
Karolinska institutet.
Göteborgs universitet.
Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
Karolinska institutet.
Show others and affiliations
2011 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 38, 33084-94 p.Article in journal (Refereed) Published
Abstract [en]

Bone destruction is the major pathological process in many bone metabolic diseases and is a result of increased osteoclast formation and bone resorption. The liver X receptors (α,β), important regulators of cholesterol metabolism and inflammatory signaling, have recently been observed to play a role in both physiological and pathological bone turnover. However, the relationship between liver X receptors (LXR) and osteoclast differentiation/formation remains unknown. Here, we report that the LXR ligand GW3965 is able to clearly and potently inhibit the formation of mature osteoclasts from receptor activator of nuclear factor κB ligand (RANKL)-stimulated human and murine osteoclast precursors. This results in a significant inhibition of bone resorption. We observed that GW3965 significantly inhibited expression of the osteoclast markers tartrate-resistant acid phosphatase, cathepsin K, osteoclast-associated receptor (OSCAR), and calcitonin receptor, appearing to act in an NFATc1/p38/microphthalmia-associated transcription factor (MITF)-dependent mechanism, independently of receptor activator of nuclear factor κB or c-Fos and not directly involving the NFκB pathways. GW3965 was less effective in RAW264.7 monocyte/macrophage cells, which are more committed into the osteoclast lineage. Also, GW3965 seemed to act differently depending on the source of the progenitor cells as it had no effect on calvarial osteoclasts, compared with marrow or blood-derived monocytes. As these effects were abolished in osteoclast precursors derived from LXRβ(-/-) mice, we suggest that GW3965 acts via an LXRβ-dependent mechanism. Taken together, our results suggest that the LXR can act as an important inhibitor of RANKL-mediated osteoclast differentiation.

Place, publisher, year, edition, pages
Bethesda, Md.: American Society for Biochemistry and Molecular Biology , 2011. Vol. 286, no 38, 33084-94 p.
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-47561DOI: 10.1074/jbc.M111.235937PubMedID: 21784849OAI: oai:DiVA.org:umu-47561DiVA: diva2:442984
Available from: 2011-09-23 Created: 2011-09-23 Last updated: 2017-12-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Lerner, Ulf H
By organisation
Molecular Periodontology
In the same journal
Journal of Biological Chemistry
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 51 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf