title: Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice.
abstract: Chemerin is an adipokine that regulates adipogenesis and metabolic functions of mature adipocytes mainly through the activation of chemokine-like receptor 1 (CMKLR1). Elevated levels of chemerin have been found in individuals with obesity, type 2 diabetes, and osteoporosis. This adipokine was identified as an inflammatory and metabolic syndrome marker. Considering that the association between metabolic syndrome and bone health remains unclear, the present study aimed to clarify the role of chemerin in the pathophysiology of bone loss induced by dyslipidemia, particularly modulating osteoclastogenesis. In vitro analyses showed a downregulation of CMKLR1 at the early stage of differentiation and a gradual increase at late stages. Strikingly, chemerin did not modify osteoclast differentiation markers or osteoclast formation; however, it increased the actin-ring formation and bone resorption activity in mature osteoclasts. The increased bone resorption activity induced by chemerin was effectively inhibited by CMKLR1 antagonist (CCX832). Chemerin boosting mature osteoclast activity involves ERK5 phosphorylation. Moreover, two models of dyslipidemia (high-fat diet [HFD]-treated C57/BL6 and db/db mice) exhibited significantly increased level of chemerin in the serum and gingival tissue. Morphometric analysis showed that HFD-treated and db/db mice exhibited increased alveolar bone loss compared to respective control mice, which was associated with an up-regulation of chemerin, CMKLR1 and cathepsin K mRNA expression in the gingival tissue. The treatment of db/db mice with CCX832 effectively inhibited bone loss. Antagonism of chemerin receptor also inhibited the expression of cathepsin K in the gingival tissue. Our results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, Department of Physics and Chemistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Erivan S
authors.initials: ES
authors.lastname: Ramos-Junior
authors.affiliation: School of Dentistry of Ribeirao Preto, Department of Pediatric Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Gisele A
authors.initials: GA
authors.lastname: Leite
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, Department of Physics and Chemistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Cecilia C
authors.initials: CC
authors.lastname: Carmo-Silva
authors.affiliation: School of Dentistry of Ribeirao Preto, Department of Pediatric Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Thaise M
authors.initials: TM
authors.lastname: Taira
authors.affiliation: School of Medicine of Ribeirao Preto, Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Karla B
authors.initials: KB
authors.lastname: Neves
authors.affiliation: School of Medicine of Ribeirao Preto, Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: David F
authors.initials: DF
authors.lastname: Colón
authors.affiliation: School of Dentistry of Ribeirao Preto, Department of Pediatric Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Lea Ab
authors.initials: LA
authors.lastname: da Silva
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, Department of Clinical Analyses, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Sergio L
authors.initials: SL
authors.lastname: Salvador
authors.affiliation: School of Medicine of Ribeirao Preto, Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: School of Medicine of Ribeirao Preto, Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: School of Pharmaceutical Sciences of Ribeirao Preto, Department of Physics and Chemistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Fukada
mesh_terms: D016301:Alveolar Bone Loss / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D050171:Dyslipidemias / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: C486456:CMKLR1 protein, mouse; D018925:Chemokines; D004041:Dietary Fats; D036341:Intercellular Signaling Peptides and Proteins; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse
keywords: ADIPOKINE; CHEMERIN; DYSLIPIDEMIA; METABOLISM; OSTEOCLASTS