Efficient gene transfer to periodontal ligament cells and human gingival fibroblasts by adeno-associated virus vectors

Kunze, Melanie; Huber, Anke; Krajewski, Anna C.; Lowden, Esther; Schuhmann, Natascha K.; Buening, Hildegard; Hallek, Michael; Noack, Michael; Perabò, Luca

doi:10.1016/j.jdent.2009.03.001

Cited by 14 publications

(12 citation statements)

References 42 publications

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“…The infection with 1×10 5 AAV2-EGFP particles induced a high frequency of cells that expressed the target protein, and the infection with AAV2-BMP-7 promoted the long-term expression of BMP-7 in DPCs, which is consistent with the notion that the dental cells are quite sensitive to adeno-associated virus infections 23) . Furthermore, this induction of BMP-7 did not alter the dynamics of the proliferation and viability of infected cells, which suggests that the generated AAV2-BMP-7 has a high infectivity and a low cytotoxicity.…”

Section: Discussionsupporting

confidence: 81%

Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

et al. 2014

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This present study investigated the potential of adeno-associated virus serotype 2 (AAV2) mediated BMP-7 (AAV2-BMP-7) to induce odontoblastic differentiation of human dental pulp cells (DPCs) in vitro. AAV2-BMP-7 was constructed to overexpress BMP-7, and the biologic effects of BMP-7 on DPCs were investigated by the evaluation of the activity of alkaline phosphatase (ALPase), the detection of the expression of dentin sialophosphoprotein (DSPP) and osteocalcin (OCN) expression and the analysis of the proliferative ability of the cells. DPCs that were infected with AAV2-BMP-7 displayed significantly upregulated ALP activity and formed mineralized nodules. Moreover, AAV2-BMP-7 promoted the expression of mineralization-related genes, which included DSPP and OCN. In addition, there was no significant difference between the proliferative ability of AAV2-BMP-7 and the control group. In conclusion, AAV2-BMP-7 promoted the odontoblastic differentiation in DPCs, a clear indication of the therapeutic potential of AAV2-BMP-7 in dental tissue regeneration.

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Section: Discussionsupporting

confidence: 81%

Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

et al. 2014

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“…In periodontal disease, AAV2 achieved the highest transduction rates for human primary periodontal ligament cells as well as periodontal tissues (Kunze et al. ). On the basis of our study, we believe that AAV‐mediated Ac45 knockdown can be employed as a novel and effective periodontitis therapy.…”

Section: Discussionmentioning

confidence: 99%

Ac45 silencing mediated by AAV‐sh‐Ac45‐RNAi prevents both bone loss and inflammation caused by periodontitis

Zhu

Chen

Hao

et al. 2015

J Clinic Periodontology

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Aim Periodontitis induced by oral pathogens leads to severe periodontal tissue damage and osteoclast-mediated bone resorption caused by inflammation. Based on the importance of Ac45 in osteoclast formation and function, we performed this study to evaluate the therapeutic potential of periodontitis by local adeno-associated virus (AAV)-mediated Ac45 gene knockdown. Material and Methods We used AAV-mediated short hairpin RNAi knockdown of Ac45 gene expression (AAV-sh-Ac45) to inhibit bone erosion and gingival inflammation simultaneously in a well-established periodontitis mouse model induced by Porphyromonas gingivalis W50. Histological studies were performed to evaluate the bone protection of AAV-sh-Ac45. Immunochemistry, ELISA and qRT-PCR were performed to reveal the role of Ac45 knockdown on inflammation, immune response and expression of cytokine. Results We found that Ac45 knockdown impaired osteoclast-mediated extracellular acidification and bone resorption in vitro and in vivo. Furthermore, local administration of AAV-sh-Ac45 protected mice from bone erosion by >85% and attenuated inflammation and decreased infiltration of T-cells, dendritic cells and macrophages in the periodontal lesion. Notably, the expression of pro-inflammatory cytokines was also reduced. Conclusions Local AAV-sh-Ac45 gene therapy efficiently protects against periodontal tissue damage and bone erosion through both inhibition of osteoclast function and attenuating inflammation, and may represent a powerful new treatment strategy for periodontitis.

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“…It has been reported that AAV gene transfer of mitogen-activated protein kinase phosphatase-1 (MKP-1), which dephosphorylates MAPKs and inhibits immune responses, inhibits periodontal bone loss in a rat model of periodontal disease (40). AAV2 also achieved the highest transduction rates for human primary periodontal ligament cells, as well as periodontal tissues (41). Transduction of gingival tissues with AAV/2/1-TNF Receptor: Fc reduced P. gingivalis induced periodontal bone loss by approximately 50% in a mouse model, with concomitant reductions in proinflammatory cytokines and osteoclasts (42).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that periodontal disease not only leads to the loss of teeth, but that it is also associated in epidemiologic studies with atherosclerosis, coronary artery disease, premature birth, stroke and rheumatoid arthritis, presumably by contributing to overall levels of systemic inflammation (41, 44–46). Oral microorganisms have also been linked to infections of the endocardium, meninges, mediastinum, vertebrae, hepatobiliary system and prosthetic joints (2, 47–48).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

et al. 2013

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Regulator of G-protein Signaling 10 (Rgs10) plays an important function in osteoclast differentiation. However, the role of Rgs10 in immune cells and inflammatory responses, which activate osteoclasts in inflammatory lesions, such as bacteria-induced periodontal disease lesions, remains largely unknown. In this study, we used an adeno-associated virus (AAV-) mediated RNAi (AAV-shRNA-Rgs10) knockdown approach to study Rgs10’s function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease. We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption, in vitro and in vivo. Interestingly, local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells, T-cells and osteoclasts, and protected the periodontal tissues from local inflammatory damage and bone destruction. Importantly, AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgs10 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and activation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.

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Efficient gene transfer to periodontal ligament cells and human gingival fibroblasts by adeno-associated virus vectors

Cited by 14 publications

References 42 publications

Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

Ac45 silencing mediated by AAV‐sh‐Ac45‐RNAi prevents both bone loss and inflammation caused by periodontitis

Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

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