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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) GEHC MicroView software with Analysis + software to generate VOI on the 2, 3, and 4 metatarsal joints for BMD assessment. Panel (b) summarizes the bone mineral density readings among groups. OPG gene transfer significantly preserved the subchondral BMD compared to the untreated and LacZ-gene controls (P < 0.05).
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fig5: (a) GEHC MicroView software with Analysis + software to generate VOI on the 2, 3, and 4 metatarsal joints for BMD assessment. Panel (b) summarizes the bone mineral density readings among groups. OPG gene transfer significantly preserved the subchondral BMD compared to the untreated and LacZ-gene controls (P < 0.05).

Mentions: MicroCT analysis was performed to quantify the subchondral bone mineral density (BMD) changes among groups of arthritic paws. Figure 5(a) illustrates an example of the 3-D VOI on an arthritic paw CT image, and the analysis suggested that OPG gene transduction effectively protected against the subchondral bone degradation of the arthritic paws compared to the controls (Figure 5(b), *P < 0.05).


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) GEHC MicroView software with Analysis + software to generate VOI on the 2, 3, and 4 metatarsal joints for BMD assessment. Panel (b) summarizes the bone mineral density readings among groups. OPG gene transfer significantly preserved the subchondral BMD compared to the untreated and LacZ-gene controls (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: (a) GEHC MicroView software with Analysis + software to generate VOI on the 2, 3, and 4 metatarsal joints for BMD assessment. Panel (b) summarizes the bone mineral density readings among groups. OPG gene transfer significantly preserved the subchondral BMD compared to the untreated and LacZ-gene controls (P < 0.05).
Mentions: MicroCT analysis was performed to quantify the subchondral bone mineral density (BMD) changes among groups of arthritic paws. Figure 5(a) illustrates an example of the 3-D VOI on an arthritic paw CT image, and the analysis suggested that OPG gene transduction effectively protected against the subchondral bone degradation of the arthritic paws compared to the controls (Figure 5(b), *P < 0.05).

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