PMID- 22154615 OWN - NLM STAT- MEDLINE DCOM- 20130701 LR - 20200205 IS - 1778-7254 (Electronic) IS - 1297-319X (Linking) VI - 79 IP - 5 DP - 2012 Oct TI - Adeno-associated virus-mediated osteoprotegerin gene transfer protects against joint destruction in a collagen-induced arthritis rat model. PG - 482-7 LID - S1297-319X(11)00272-7 [pii] LID - 10.1016/j.jbspin.2011.10.011 [doi] AB - 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 muL/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-1beta was not significant; the scores of pannus and inflammation in rAAV-hOPG group have no significant difference. CONCLUSION: 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. CI - Copyright (c) 2011. Published by Elsevier SAS. FAU - Bao, Lizhi AU - Bao L AD - Rheumatology and Immunology Department, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China. FAU - Zhu, Tingting AU - Zhu T FAU - Zhao, Dongbao AU - Zhao D FAU - Han, Xinhai AU - Han X FAU - Guan, Jianlong AU - Guan J FAU - Shi, Zhiqing AU - Shi Z FAU - Zhang, Lanlin AU - Zhang L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111209 PL - France TA - Joint Bone Spine JT - Joint bone spine JID - 100938016 RN - 0 (Interleukin-1beta) RN - 0 (Osteoprotegerin) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Arthritis, Experimental/metabolism/pathology/*prevention & control MH - Arthrography MH - Dependovirus/*genetics MH - Disease Models, Animal MH - Gene Transfer Techniques MH - Genetic Therapy/*methods MH - Interleukin-1beta/metabolism MH - Joints/metabolism/*pathology MH - Male MH - Matrix Metalloproteinase 3/metabolism MH - Osteoprotegerin/*genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley EDAT- 2011/12/14 06:00 MHDA- 2013/07/03 06:00 CRDT- 2011/12/14 06:00 PHST- 2011/06/07 00:00 [received] PHST- 2011/10/03 00:00 [accepted] PHST- 2011/12/14 06:00 [entrez] PHST- 2011/12/14 06:00 [pubmed] PHST- 2013/07/03 06:00 [medline] AID - S1297-319X(11)00272-7 [pii] AID - 10.1016/j.jbspin.2011.10.011 [doi] PST - ppublish SO - Joint Bone Spine. 2012 Oct;79(5):482-7. doi: 10.1016/j.jbspin.2011.10.011. Epub 2011 Dec 9.