title: Acetylated derivative of glaucine inhibits joint inflammation in collagenase-induced arthritis.
abstract: BACKGROUND
  Osteoarthritis (OA) has become by far the most common joint disorder. A number of studies using OA animal models have explored the effects of agents that can modulate bone metabolism.
  
  
  OBJECTIVE
  In the present study, we investigated the effect of acetylated derivative of plant alkaloid glaucine (ADG) on experimental OA in mice.
  
  
  METHODS
  Arthritis was induced by two intraarticular (i.a.) injections of collaganase. Histopathological changes were observed through hematoxylin and eosine (H&E), safranin O and toluidine blue staining. Differentiation of bone marrow (BM) cells was evaluated by tartarate-resistant acid phosphatase (TRAP) assay. The expression of phospho-Janus kinase 2 (pJAK2) and phospho signal transducer and activator of transcription3 (pSTAT3) expression in the joints was determined by immunohistochemistry.
  
  
  RESULTS
  We established that ADG significantly decreased cell infiltration (2.32 ± 0.14 versus 1.62 ± 0.13), cartilage loss (2.42 ± 0.12 versus 1.12 ± 0.10) and bone erosion (1.76 ± 0.13 versus 1.04 ± 0.14) in arthritic mice. It appeared that the substance inhibited in a dose-dependent manner osteoclast differentiation in vitro. ADG suppressed the expression of pJAK2 in the joint and partially affected the expression of pSTAT3.
  
  
  CONCLUSIONS
  Present results suggest that ADG is a suitable candidate for further development as an anti-arthritic agent.
authors.affiliation: Department of Immunology, Institute of Microbiology , Sofia , Bulgaria and.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Gyurkovska
authors.forename: Stefan
authors.initials: S
authors.lastname: Philipov
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Kostova
authors.forename: Nina
authors.initials: N
authors.lastname: Ivanovska
mesh_terms: D000107:Acetylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001060:Aporphines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007596:Joints / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D003012:Microbial Collagenase / Q000494:pharmacology*; D015394:Molecular Structure; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001060:Aporphines; D003012:Microbial Collagenase; C005004:glaucine
keywords: Acetylated derivative of glaucine; JAK–STAT pathway; collagenase-induced osteoarthritis; osteoclastogenesis; proteoglycans