title: Adrenomedullin(22-52)  combats inflammation and prevents systemic bone loss in murine collagen-induced arthritis.
abstract: OBJECTIVE
  Adrenomedullin(22-52)  is a truncated peptide derived from adrenomedullin, a growth factor with antiapoptotic and immunoregulatory properties. It can act as an agonist or an antagonist depending on cell type. Its in vivo effects are unknown, but adrenomedullin(22-52)  could possess immunomodulatory properties. This study was undertaken to evaluate the effect of adrenomedullin(22-52)  in a mouse model of arthritis.
  
  
  METHODS
  DBA/1 mice with collagen-induced arthritis (CIA) were treated with 1.2 μg/gm adrenomedullin(22-52) , adrenomedullin, or saline at arthritis onset. Bone mineral density was measured at the beginning of the experiment and when mice were killed. Mouse joints were processed for histologic analysis and protein studies, and spleens were examined for Treg cell expression. Cytokine expression was studied in mouse joint tissue and serum.
  
  
  RESULTS
  In mice with CIA, adrenomedullin and adrenomedullin(22-52)  reduced clinical and histologic arthritis scores and shifted the pattern of articular and systemic cytokine expression from Th1 to Th2, as compared to untreated mice with CIA (controls). Tumor necrosis factor α, interleukin-6 (IL-6), and IL-17A levels were significantly decreased in the joints of mice with CIA treated with adrenomedullin or adrenomedullin(22-52)  as compared to controls, whereas IL-4 and IL-10 levels were increased. Adrenomedullin(22-52)  was more effective than adrenomedullin in modulating cytokine content and enhanced Treg cell function without changing Treg cell expression compared to controls. Adrenomedullin receptor binding and transcriptional adrenomedullin receptor expression were markedly increased in joints from controls, whereas adrenomedullin receptor binding was considerably decreased in treated animals. Mice with CIA treated with adrenomedullin or adrenomedullin(22-52)  had considerably fewer apoptotic chondrocytes and diminished cartilage degradation. Adrenomedullin(22-52)  completely prevented systemic bone loss by preserving osteoblastic activity, but without changes in osteoclastic activity.
  
  
  CONCLUSIONS
  Our findings indicate that adrenomedullin(22-52) , which has no vasoactive or tumor-inducing effects, is a potent antiinflammatory and bone-protective agent in this arthritis model.
authors: INSERM, UMR-S 606, Hôpital Lariboisière, AP-HP, Université Paris Diderot, Paris, France.
authors: Marie-Dominique
authors: MD
authors: Ah Kioon
authors: Carine
authors: C
authors: Asensio
authors: Hang-Korng
authors: HK
authors: Ea
authors: Frédéric
authors: F
authors: Velard
authors: Benjamin
authors: B
authors: Uzan
authors: Sandrine
authors: S
authors: Rullé
authors: Céline
authors: C
authors: Bazille
authors: Caroline
authors: C
authors: Marty
authors: Géraldine
authors: G
authors: Falgarone
authors: Christelle
authors: C
authors: Nguyen
authors: Corinne
authors: C
authors: Collet
authors: Jean-Marie
authors: JM
authors: Launay
authors: Martine
authors: M
authors: Cohen-Solal
authors: Frédéric
authors: F
authors: Lioté
mesh_terms: D053607:Adrenomedullin / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D058265:Receptors, Adrenomedullin / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D010446:Peptide Fragments; D058265:Receptors, Adrenomedullin; C104782:adrenomedullin (22-52); D053607:Adrenomedullin