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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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(a)–(c) Typical histological appearance of CIA mouse paws: (a) severe inflammatory cellular infiltration—synovitis and pannus formation; (b) bone and cartilage erosion; (c) toluidine blue stained section showing destruction of articular cartilage with loss of joint space and complete architecture distortion. Panels (d)–(f), example histological images of mouse paws after OPG gene modification: joint space was maintained and dramatically less bone and cartilage damage were obvious. (f) A Toluidine Blue stained paw section showing the protection effect on articulating cartilage.
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fig3: (a)–(c) Typical histological appearance of CIA mouse paws: (a) severe inflammatory cellular infiltration—synovitis and pannus formation; (b) bone and cartilage erosion; (c) toluidine blue stained section showing destruction of articular cartilage with loss of joint space and complete architecture distortion. Panels (d)–(f), example histological images of mouse paws after OPG gene modification: joint space was maintained and dramatically less bone and cartilage damage were obvious. (f) A Toluidine Blue stained paw section showing the protection effect on articulating cartilage.

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)

(a)–(c) Typical histological appearance of CIA mouse paws: (a) severe inflammatory cellular infiltration—synovitis and pannus formation; (b) bone and cartilage erosion; (c) toluidine blue stained section showing destruction of articular cartilage with loss of joint space and complete architecture distortion. Panels (d)–(f), example histological images of mouse paws after OPG gene modification: joint space was maintained and dramatically less bone and cartilage damage were obvious. (f) A Toluidine Blue stained paw section showing the protection effect on articulating cartilage.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: (a)–(c) Typical histological appearance of CIA mouse paws: (a) severe inflammatory cellular infiltration—synovitis and pannus formation; (b) bone and cartilage erosion; (c) toluidine blue stained section showing destruction of articular cartilage with loss of joint space and complete architecture distortion. Panels (d)–(f), example histological images of mouse paws after OPG gene modification: joint space was maintained and dramatically less bone and cartilage damage were obvious. (f) A Toluidine Blue stained paw section showing the protection effect on articulating cartilage.
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