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


METHODS
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)-kappaB activation and Akt phosphorylation were determined with western blotting. Lipid mediator production was assessed with liquid chromatography tandem mass spectrometry.


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-kappaB ligand-induced nuclear translocation of the p50 subunit of NF-kappaB. 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 [(3)H]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
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.
Herrera
B S
BS
Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 2118, USA.
Ohira
T
T
Gao
L
L
Omori
K
K
Yang
R
R
Zhu
M
M
Muscara
M N
MN
Serhan
C N
CN
Van Dyke
T E
TE
Gyurko
R
R
D000818:Animals; D017209:Apoptosis; D001862:Bone Resorption; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003804:Dentin / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control*; D007975:Leukotriene B4 / Q000096:biosynthesis; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D011869:Radioligand Assay
D007975:Leukotriene B4; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid