Resolvin El and Chemokine-like Receptor 1 Mediate Bone Preservation.

The polyunsaturated ω-3 fatty acid eicosapentaenoic acid-derived resolvin EI (RvEl) enhances resolution of inflammation, prevents bone loss, and induces bone regeneration. Although the inflammation-resolving actions of RvEl are characterized, the molecular mechanism of its bone-protective actions are of interest. To test the hypothesis that receptor-mediated events impact bone changes, we prepared transgenic mice overexpressing the RvEl receptor chemokine-like receptor 1 (chemR23) on leukocytes. In zymosan-initiated peritonitis, neutrophil polymorphonuclear leukocyte infiltration in response to RvEl was limited requiring log order lower doses in chemR23tg mice. Ligature-induced alveolar bone loss was diminished in chemR23tg mice. Local RvEl treatment of uniform craniotomy in the parietal bone significantly accelerated regeneration of the bone defect. In in vitro bone cultures, RvEl significantly enhanced expression of osteoprotegerin (OPG) without inducing change in receptor activator of NF-KB ligand levels, whereas the osteogenic markers alkaline phosphatase, bone sialoprotein, and Runt-related transcription factor 2 remained unchanged. These results indicate that RvEl modulates osteoclast differentiation and bone remodeling by direct actions on bone, rescuing OPG production and restoring a favorable receptor activator of NF-KB ligand/OPG ratio, in addition to known anti-inflammatory and proresolving actions. [ABSTRACT FROM AUTHOR]