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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

Gene expression profiles of the arthritic joint tissues following OPG gene transfer. The data are expressed as percentage changes of the comparative gene copies against readings from the LacZ-control gene transduced tissues. No mRNA expression change is expressed as 0.
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fig6: Gene expression profiles of the arthritic joint tissues following OPG gene transfer. The data are expressed as percentage changes of the comparative gene copies against readings from the LacZ-control gene transduced tissues. No mRNA expression change is expressed as 0.

Mentions: Real-time PCR data suggested that there were significantly diminished mRNA expressions of TRAP, RANK, MMP3, and INFγ in the OPG-gene modified paw tissues, in comparison to the controls (Figure 6). While there was no significant influence of OPG gene transfer on TNF and IL-6 expression, in the local paw tissue, there was a reduction trend of IL-1 mRNA expression (P = 0.085).


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)

Gene expression profiles of the arthritic joint tissues following OPG gene transfer. The data are expressed as percentage changes of the comparative gene copies against readings from the LacZ-control gene transduced tissues. No mRNA expression change is expressed as 0.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Gene expression profiles of the arthritic joint tissues following OPG gene transfer. The data are expressed as percentage changes of the comparative gene copies against readings from the LacZ-control gene transduced tissues. No mRNA expression change is expressed as 0.
Mentions: Real-time PCR data suggested that there were significantly diminished mRNA expressions of TRAP, RANK, MMP3, and INFγ in the OPG-gene modified paw tissues, in comparison to the controls (Figure 6). While there was no significant influence of OPG gene transfer on TNF and IL-6 expression, in the local paw tissue, there was a reduction trend of IL-1 mRNA expression (P = 0.085).

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