title: Adeno-associated virus-mediated osteoprotegerin gene transfer protects against joint destruction in a collagen-induced arthritis rat model.
abstract: OBJECTIVE
  To evaluate the in vivo joint protection effect of recombinant adeno-associated virus-mediated gene transfer of human osteoprotegerin (rAAV-hOPG).
  
  
  METHODS
  Collagen-induced arthritis (CIA) rat model was established. CIA rats were randomly divided into three groups: CIA control group (PBS), rAAV-EGFP (enhanced green fluorescent protein) group and rAAV-hOPG (100 μL/d) group, which received corresponding intra-articular injection treatment. The thickness of the palms and soles, arthritis index, radiological score, pathological score, bone damage factor and protein expression of inflammatory factors were measured and compared with normal control group rats.
  
  
  RESULTS
  Positive fluorescence of frozen section confirmed that rAAV-hOPG was efficiently transduced into the synovial tissues of test rats. In rAAV-hOPG group compared with CIA control group, the radiological score was 30.18% lower (P<0.05); the expression of OPG protein was 93.41% higher (P<0.05); the expression of matrix metalloproteinase-3 (MMP-3) protein was 35.38% lower (P<0.05); however, the expression of IL-1β was not significant; the scores of pannus and inflammation in rAAV-hOPG group have no significant difference.
  
  
  CONCLUSIONS
  These results suggest that adeno-associated virus-mediated transfer of human osteoprotegerin is effectively transducted into the synovial tissues of CIA model, and protects against articular cartilage and bone destruction, but has no obvious efficiency on inflammation. The results also demonstrate that gene transfer using rAAV-hOPG may be a feasible and effective therapeutic candidate to treat or prevent joint destruction in inflammatory arthritis.
authors.affiliation: Rheumatology and Immunology Department, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Bao
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhu
authors.forename: Dongbao
authors.initials: D
authors.lastname: Zhao
authors.forename: Xinhai
authors.initials: X
authors.lastname: Han
authors.forename: Jianlong
authors.initials: J
authors.lastname: Guan
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Shi
authors.forename: Lanlin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001175:Arthrography; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D053583:Interleukin-1beta / Q000378:metabolism; D007596:Joints / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053583:Interleukin-1beta; D053244:Osteoprotegerin; D019278:Matrix Metalloproteinase 3