title: Resolvin E1 and chemokine-like receptor 1 mediate bone preservation.
abstract: The polyunsaturated ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1) enhances resolution of inflammation, prevents bone loss, and induces bone regeneration. Although the inflammation-resolving actions of RvE1 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 RvE1 receptor chemokine-like receptor 1 (chemR23) on leukocytes. In zymosan-initiated peritonitis, neutrophil polymorphonuclear leukocyte infiltration in response to RvE1 was limited requiring log order lower doses in chemR23tg mice. Ligature-induced alveolar bone loss was diminished in chemR23tg mice. Local RvE1 treatment of uniform craniotomy in the parietal bone significantly accelerated regeneration of the bone defect. In in vitro bone cultures, RvE1 significantly enhanced expression of osteoprotegerin (OPG) without inducing change in receptor activator of NF-κB ligand levels, whereas the osteogenic markers alkaline phosphatase, bone sialoprotein, and Runt-related transcription factor 2 remained unchanged. These results indicate that RvE1 modulates osteoclast differentiation and bone remodeling by direct actions on bone, rescuing OPG production and restoring a favorable receptor activator of NF-κB ligand/OPG ratio, in addition to known anti-inflammatory and proresolving actions.
authors.affiliation: Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Dan
authors.initials: D
authors.lastname: Faibish
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Fredman
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Herrera
authors.forename: Nan
authors.initials: N
authors.lastname: Chiang
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
authors.forename: Robert
authors.initials: R
authors.lastname: Gyurko
mesh_terms: D016301:Alveolar Bone Loss / Q000235:genetics; D000818:Animals; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010518:Periodontitis / Q000235:genetics / Q000378:metabolism; D010529:Peritoneal Cavity; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
chemical_list: C102741:CMKLR1 protein, human; D053244:Osteoprotegerin; D019707:Receptors, Chemokine; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid