title: The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation.
abstract: BACKGROUND
  The purpose of this study was to evaluate the effects of risedronate (Ris) in the modulation of bone formation in rats with glucocorticoid (GC)-induced osteoporosis by histomorphometric, immunohistochemical and gene expression analyses.
  
  
  METHODS
  We analyzed structure, turnover and microarchitecture, cyclooxygenase 2 (COX-2) levels and osteocyte apoptosis in 40 female rats divided as follows: 1) vehicle of methylprednisolone (vGC) + vehicle of risedronate (vRis); 2) Ris 5 μg/Kg + vGC; 3) methylprednisolone (GC) 7 mg/Kg + vRis; 4) GC 7 mg/Kg +Ris 5 μg/Kg. In addition, we evaluated cell proliferation and expression of COX-2 and bone alkaline phosphatase (b-ALP) genes in bone marrow cells and MLO-y4 osteocytes treated with Ris alone or in co-treatment with the selective COX-2 inhibitor NS-398 or with dexametasone.
  
  
  RESULTS
  Ris reduced apoptosis induced by GC of osteocytes (41% vs 86%, P < 0.0001) and increased COX-2 expression with respect to controls (Immuno-Hystochemical Score (IHS): 8.75 vs 1.00, P < 0.0001). These positive effects of Ris in bone formation were confirmed by in vitro data as the viability and expression of b-ALP gene in bone marrow cells resulted increased in a dose dependent manner.
  
  
  CONCLUSIONS
  These findings suggest a positive effect of Ris in bone formation and support the hypothesis that the up-regulation of COX-2 could be an additional mechanism of anabolic effect of Ris.
authors.affiliation: Department of Medicine, University of Verona Piazzale L, Scuro, Verona, Italy. mariateresa.valenti@univr.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenti
authors.forename: Sandro
authors.initials: S
authors.lastname: Giannini
authors.forename: Luca
authors.initials: L
authors.lastname: Donatelli
authors.forename: Mirko
authors.initials: M
authors.lastname: Zanatta
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoldo
authors.forename: Stefania
authors.initials: S
authors.lastname: Sella
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vilei
authors.forename: Elena
authors.initials: E
authors.lastname: Ossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Realdi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lo Cascio
authors.forename: Luca
authors.initials: L
authors.lastname: Dalle Carbonare
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics*; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D051546:Cyclooxygenase 2; D000068296:Risedronic Acid; D012968:Etidronic Acid