An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption

B. S. Herrera, T. Ohira, L. Gao, Kazuhiro Omori, R. Yang, M. Zhu, M. N. Muscara, C. N. Serhan, T. E. Van Dyke, R. Gyurko

Research output: Contribution to journalArticle

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Abstract

Background and purpose: The inflammation-resolving lipid mediator resolvin E1 (RvE1) effectively stops inflammation-induced bone loss in vivo in experimental periodontitis. It was of interest to determine whether RvE1 has direct actions on osteoclast (OC) development and bone resorption. Experimental approach: Primary OC cultures derived from mouse bone marrow were treated with RvE1 and analysed for OC differentiation, cell survival and bone substrate resorption. Receptor binding was measured using radiolabelled RvE1. Nuclear factor (NF)-κB activation and Akt phosphorylation were determined with western blotting. Lipid mediator production was assessed with liquid chromatography tandem mass spectrometry. Key results: OC growth and resorption pit formation were markedly decreased in the presence of RvE1. OC differentiation was inhibited by RvE1 as demonstrated by decreased number of multinuclear OC, a delay in the time course of OC development and attenuation of receptor activator of NF-κB ligand-induced nuclear translocation of the p50 subunit of NF-κB. OC survival and apoptosis were not altered by RvE1. Messenger RNA for both receptors of RvE1, ChemR23 and BLT 1 is expressed in OC cultures. Leukotriene B 4 (LTB 4) competed with [ 3H]RvE1 binding on OC cell membrane preparations, and the LTB 4 antagonist U75302 prevented RvE1 inhibition of OC growth, indicating that BLT 1 mediates RvE1 actions on OC. Primary OC synthesized the RvE1 precursor 18R-hydroxy-eicosapentaenoic acid and LTB 4. Co-incubation of OC with peripheral blood neutrophils resulted in transcellular RvE1 biosynthesis. Conclusions and implications: These results indicate that RvE1 inhibits OC growth and bone resorption by interfering with OC differentiation. The bone-sparing actions of RvE1 are in addition to inflammation resolution, a direct action in bone remodelling.

Original languageEnglish
Pages (from-to)1214-1223
Number of pages10
JournalBritish Journal of Pharmacology
Volume155
Issue number8
DOIs
Publication statusPublished - Dec 25 2008
Externally publishedYes

Fingerprint

Osteoclasts
Bone Resorption
Inflammation
Leukotriene B4
5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
Growth
Lipids
Osteitis
Hydroxy Acids
Eicosapentaenoic Acid
Bone Remodeling
Periodontitis
Cytoplasmic and Nuclear Receptors
Tandem Mass Spectrometry
Liquid Chromatography

Keywords

  • Cell differentiation
  • Inflammation resolution
  • Lipid mediators
  • Osteoclasts

ASJC Scopus subject areas

  • Pharmacology

Cite this

An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. / Herrera, B. S.; Ohira, T.; Gao, L.; Omori, Kazuhiro; Yang, R.; Zhu, M.; Muscara, M. N.; Serhan, C. N.; Van Dyke, T. E.; Gyurko, R.

In: British Journal of Pharmacology, Vol. 155, No. 8, 25.12.2008, p. 1214-1223.

Research output: Contribution to journalArticle

Herrera, BS, Ohira, T, Gao, L, Omori, K, Yang, R, Zhu, M, Muscara, MN, Serhan, CN, Van Dyke, TE & Gyurko, R 2008, 'An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption', British Journal of Pharmacology, vol. 155, no. 8, pp. 1214-1223. https://doi.org/10.1038/bjp.2008.367
Herrera, B. S. ; Ohira, T. ; Gao, L. ; Omori, Kazuhiro ; Yang, R. ; Zhu, M. ; Muscara, M. N. ; Serhan, C. N. ; Van Dyke, T. E. ; Gyurko, R. / An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. In: British Journal of Pharmacology. 2008 ; Vol. 155, No. 8. pp. 1214-1223.
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AU - Ohira, T.

AU - Gao, L.

AU - Omori, Kazuhiro

AU - Yang, R.

AU - Zhu, M.

AU - Muscara, M. N.

AU - Serhan, C. N.

AU - Van Dyke, T. E.

AU - Gyurko, R.

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