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Local gene transfer of OPG prevents joint damage and disease progression in collagen-induced arthritis.

Zhang Q, Gong W, Ning B, Nie L, Wooley PH, Yang SY - ScientificWorldJournal (2013)

Bottom Line: A single periarticular injection of AAV-OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks.Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P < 0.05).Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P < 0.05), although treatment appeared less effective on the local inflammatory progress.

View Article: PubMed Central - PubMed

Affiliation: Orthopaedic Research Institute, Via Christi Wichita Hospitals, Wichita, KS 67214, USA ; Jinan Central Hospital, Shandong University, Jinan 250013, China.

ABSTRACT
This study examined the influence of osteoprotegerin (OPG) gene transfer on a murine collagen-induced arthritis model. A single periarticular injection of AAV-OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks. Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P < 0.05). Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P < 0.05), although treatment appeared less effective on the local inflammatory progress. MicroCT data suggested significant protection against subchondral bone mineral density changes in OPG treated CIA mice. Interestingly, mRNA expressions of IFN-g and MMP3 were noticeably diminished following OPG gene transfer. Overall, gene transfer of OPG effectively inhibited the arthritis-associated periarticular bone erosion and preserved the architecture of arthritic joints, and the study provides evidence that the cartilage protection of the OPG gene therapy may be associated with the down-regulation of MMP3 expression.

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Related in: MedlinePlus

Summary of histological evaluation of arthritic paws with or without OPG gene transfer. Five categories are assessed on each paw section in a blinded fashion. OPG gene modification significantly ameliorate the disease progress, especially in bone/cartilage erosion and architecture disorganization.
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Related In: Results  -  Collection


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fig4: Summary of histological evaluation of arthritic paws with or without OPG gene transfer. Five categories are assessed on each paw section in a blinded fashion. OPG gene modification significantly ameliorate the disease progress, especially in bone/cartilage erosion and architecture disorganization.

Mentions: Histological evaluation of the arthritic paws of negative control or LacZ-transduced mice revealed severe synovial inflammatory cellular infiltration and pannus formation, marked bone and cartilage erosion, and distortion of joint architecture (Figure 3). In vivo transduction of OPG dramatically protected against the cartilage and subchondral bone erosions (Figure 4, P < 0.05), although there were no significant ameliorations among the histological scores on synovitis and pannus formation, in comparison with the control animals. Toluidine staining showed that OPG gene transfer also effectively protected against the articular cartilage erosions and preserved the joint space and overall architectures (Figure 3).


Local gene transfer of OPG prevents joint damage and disease progression in collagen-induced arthritis.

Zhang Q, Gong W, Ning B, Nie L, Wooley PH, Yang SY - ScientificWorldJournal (2013)

Summary of histological evaluation of arthritic paws with or without OPG gene transfer. Five categories are assessed on each paw section in a blinded fashion. OPG gene modification significantly ameliorate the disease progress, especially in bone/cartilage erosion and architecture disorganization.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814078&req=5

fig4: Summary of histological evaluation of arthritic paws with or without OPG gene transfer. Five categories are assessed on each paw section in a blinded fashion. OPG gene modification significantly ameliorate the disease progress, especially in bone/cartilage erosion and architecture disorganization.
Mentions: Histological evaluation of the arthritic paws of negative control or LacZ-transduced mice revealed severe synovial inflammatory cellular infiltration and pannus formation, marked bone and cartilage erosion, and distortion of joint architecture (Figure 3). In vivo transduction of OPG dramatically protected against the cartilage and subchondral bone erosions (Figure 4, P < 0.05), although there were no significant ameliorations among the histological scores on synovitis and pannus formation, in comparison with the control animals. Toluidine staining showed that OPG gene transfer also effectively protected against the articular cartilage erosions and preserved the joint space and overall architectures (Figure 3).

Bottom Line: A single periarticular injection of AAV-OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks.Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P < 0.05).Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P < 0.05), although treatment appeared less effective on the local inflammatory progress.

View Article: PubMed Central - PubMed

Affiliation: Orthopaedic Research Institute, Via Christi Wichita Hospitals, Wichita, KS 67214, USA ; Jinan Central Hospital, Shandong University, Jinan 250013, China.

ABSTRACT
This study examined the influence of osteoprotegerin (OPG) gene transfer on a murine collagen-induced arthritis model. A single periarticular injection of AAV-OPG or AAV-LacZ on the arthritic paw successfully incorporated the exogenous gene to the local tissue and resulted in marked transgene expression in the joint homogenate for at least three weeks. Clinical disease scores were significantly improved in OPG treated mice starting at 28-day post-treatment (P < 0.05). Histological assessment demonstrated that OPG gene transfer dramatically protected mice from erosive joint changes compared with LacZ controls (P < 0.05), although treatment appeared less effective on the local inflammatory progress. MicroCT data suggested significant protection against subchondral bone mineral density changes in OPG treated CIA mice. Interestingly, mRNA expressions of IFN-g and MMP3 were noticeably diminished following OPG gene transfer. Overall, gene transfer of OPG effectively inhibited the arthritis-associated periarticular bone erosion and preserved the architecture of arthritic joints, and the study provides evidence that the cartilage protection of the OPG gene therapy may be associated with the down-regulation of MMP3 expression.

Show MeSH
Related in: MedlinePlus