Adenoviral vector-mediated overexpression of osteoprotegerin accelerates osteointegration of titanium implants in ovariectomized rats

Yin, Guoyong; Chen, J; Wei, Shanqiao; Wang, H; Q, Chen; Lin, Yu; Hu, Jing; Luo, En

doi:10.1038/gt.2015.34

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…Furthermore, human OPG shares 85% and 86% amino acid identity to mouse and rat OPG, respectively, indicating that the OPG has been highly conserved throughout evolution [4]. In addition, previous studies reported that the xenogeneic human OPG exerted positive effects in both mice and rats [29,30]. To our knowledge, this is the first report of reconstruction of a critical-sized bone defect in OVX rats using OPG-BMSCs seeded HA scaffolds.…”

Section: Discussionmentioning

confidence: 64%

“…It has been reported that a single IV injection of adeno-associated virus vector carrying cDNA for recombinant human OPG was able to reverse established osteopenia in OVX mice [29]. Local administration of adenoviral vector-mediated OPG could also enhance osseointegration around titanium implant in OVX rats [30]. To attain a therapeutic concentration of OPG and to achieve a long-term therapeutic effect, BMSCs were used as a gene delivery vehicle in this study.…”

Section: Discussionmentioning

confidence: 95%

“…The system of micro-CT was set to 70 kV, 114 mA, 500 ms integration time, and the scanning region had a resolution of 2048×2048 pixels and an isotropic voxel size of 10 µm for detail evaluation. A threshold value of 205 mg HA/ccm was set to distinguish mineralized tissue from the unmineralized tissue [21]. The defect of mandible was selected as the volume of interest.…”

Section: Microcomputed Tomography (Micro-ct) Scanningmentioning

confidence: 99%

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Osteoprotegerin gene-modified BMSCs with hydroxyapatite scaffold for treating critical-sized mandibular defects in ovariectomized osteoporotic rats

Liu

Bao

et al. 2016

Acta Biomaterialia

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Women with postmenopausal osteoporosis are at a high risk for fracture as their bone resorption rate exceeds bone formation rate. Osteoprotegerin (OPG), a known therapeutic agent capable of inhibiting osteoclast cells, has been used in treatment of chronic bone resorptive diseases. To inhibit excessive bone resorption and increase bone formation, we developed a novel therapeutic strategy by genetically modifying bone marrow stem cells (BMSCs) for OPG delivery and seeding the cells on a hydroxyapatite (HA) scaffold for in vivo bone defect repair. The novel OPG-BMSC-HA constructs were able to orchestrate bone-forming BMSCs and bone-resorbing osteoclasts, demonstrating good potential for osteoporosis-related bone defect reconstruction treatments.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 95%

Section: Microcomputed Tomography (Micro-ct) Scanningmentioning

confidence: 99%

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Osteoprotegerin gene-modified BMSCs with hydroxyapatite scaffold for treating critical-sized mandibular defects in ovariectomized osteoporotic rats

Liu

Bao

et al. 2016

Acta Biomaterialia

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“…In addition, AdPDGF-B used with a collagen matrix in periodontal osseous defects was considered safe for possible use in human clinical studies (Chang et al 2009). Locally delivered osteoprotegerin vector (Ad-hOPG) added to femoral defects prior to implant placement resulted in accelerated bone deposition and enhanced osseointegration of titanium implants (Yin et al 2015). A combinatory gene therapy using AdBMP7 alone or with adenovirus with LIM domain mineralization protein 3 (LMP3) gene promoted in vivo bone formation via PDL progenitor cells (Jin et al 2003;Lin et al 2013).…”

Section: Gene Therapymentioning

confidence: 99%

Regenerative Medicine for Periodontal and Peri-implant Diseases

et al. 2015

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The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions.

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“…Stable transgene expression requires the vector to be integrated into the host cell chromosome 6 7 . Unlike retroviral vectors, conventionally used adenovirus vectors can be lost with cell division, and transgene expression is thus retained for a relatively short time 8 9 . Hybrid adenovirus vectors that combine genetic elements for stabilized transgene expression and high transduction efficiencies of adenoviruses can result in mitotically stable transgene expression, in which the somatic integration can be facilitated by integrases or transposases 10 11 .…”

mentioning

confidence: 99%

Impact of Different Promoters on Episomal Vectors Harbouring Characteristic Motifs of Matrix Attachment Regions

Wang

Zhang

et al. 2016

Sci Rep

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We previously demonstrated that the characteristic sequence of matrix attachment regions (MARs) allows transgenes to be maintained episomally in CHO cells. In the present study, six commonly used promoters from human cytomegalovirus major immediate-early (CMV), simian vacuolating virus 40 (SV40), Rous sarcoma virus, Homo sapiens ubiquitin C, phosphoglycerate kinase, and β-globin, respectively, were evaluated to determine their effects on transgene expression and stability in CHO cells stably transfected via the episomal vector harbouring characteristic MAR motifs. The CHO cells were transfected with vectors and then screened using G418, after which the stably transfected cells were split into two and further cultured either in the presence or absence of G418. Of the six promoters, the CMV promoter yielded the highest transgene expression levels and the highest transfection efficiency, whereas the SV40 promoter maintained transgene expression more stably during long-term culture than the other promoters did. The CMV and SV40 promoter-containing vectors were furthermore episomally maintained and conferred sustained eGFP expression in the cells even under nonselective conditions. On the basis of these findings, we conclude that the CMV promoter performs best in terms of yielding both high expression levels and high levels of stability using this episomal vector system.

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Adenoviral vector-mediated overexpression of osteoprotegerin accelerates osteointegration of titanium implants in ovariectomized rats

Cited by 7 publications

References 32 publications

Osteoprotegerin gene-modified BMSCs with hydroxyapatite scaffold for treating critical-sized mandibular defects in ovariectomized osteoporotic rats

Osteoprotegerin gene-modified BMSCs with hydroxyapatite scaffold for treating critical-sized mandibular defects in ovariectomized osteoporotic rats

Regenerative Medicine for Periodontal and Peri-implant Diseases

Impact of Different Promoters on Episomal Vectors Harbouring Characteristic Motifs of Matrix Attachment Regions

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