Change search
ReferencesLink to record
Permanent link

Direct link
Activation of the liver X receptor-β potently inhibits osteoclastogenesis from lipopolysaccharide-exposed bone marrowderived macrophages
Umeå University, Faculty of Medicine, Department of Odontology.
2013 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 93, no 1, 71-82 p.Article in journal (Refereed) Published
Abstract [en]

Bacterial-induced bone diseases, such as periodontitis and osteomyelitis, are chronic inflammatory diseases characterized by increased bone destruction as a result of enhanced osteoclastogenesis. The LXRα and -β are important modulators of inflammatory signaling and can potently inhibit RANKL-induced osteoclast differentiation. Here, we investigated the effects of the LXR agonist GW3965 on LPS-induced osteoclast differentiation. Mouse BMMs primed with RANKL for 24 h, then exposed to LPS in the presence of GW3965 for 4 days, formed significantly fewer and smaller TRAP+-multinucleated osteoclasts with reduced expression of osteoclast markers (Acp5, Ctsk, Mmp-9, Dc-stamp, and Itgβ3), along with inhibition of actin ring development. GW3965 was able to repress proinflammatory cytokine (TNF-α, IL-1β, IL-6, and IL-12p40) expression in BMMs exposed to LPS alone; however, once BMMs entered the osteoclast lineage following RANKL priming, GW3965 no longer inhibited cytokine expression. The inhibitory action of GW3965 involved the Akt pathway but seemed to be independent of MAPKs (p38, ERK, JNK) and NF-κB signaling. GW3965 acted in a LXRβ- dependent mechanism, as osteoclast differentiation was not inhibited in BMMs derived from LXRβ-/- mice. Finally, activation of LXR also inhibited differentiation in LPS-exposed mouse RAW264.7 cells. In conclusion, GW3965 acts through LXRβ to potently inhibit osteoclast differentiation from RANKL-primed BMMs in a LPS environment. In this respect, activation of the LXR could have a beneficial, therapeutic effect in the prevention of bacterial-induced bone erosion.

Place, publisher, year, edition, pages
2013. Vol. 93, no 1, 71-82 p.
Keyword [en]
Bone resorption, Inflammation, LPS, LXR, Osteoclast
National Category
URN: urn:nbn:se:umu:diva-66228DOI: 10.1189/jlb.0712339OAI: diva2:608666
Available from: 2013-02-28 Created: 2013-02-18 Last updated: 2013-02-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Lerner, Ulf H.
By organisation
Department of Odontology
In the same journal
Journal of Leukocyte Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 37 hits
ReferencesLink to record
Permanent link

Direct link