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Ac45 silencing mediated by AAV ‐sh‐Ac45‐ RNA i prevents both bone loss and inflammation caused by periodontitis
Author(s) -
Zhu Zheng,
Chen Wei,
Hao Liang,
Zhu Guochun,
Lu Yun,
Li Sheng,
Wang Lin,
Li YiPing
Publication year - 2015
Publication title -
journal of clinical periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.456
H-Index - 151
eISSN - 1600-051X
pISSN - 0303-6979
DOI - 10.1111/jcpe.12415
Subject(s) - gene knockdown , osteoclast , inflammation , periodontitis , bone resorption , porphyromonas gingivalis , gene silencing , immunology , proinflammatory cytokine , chemistry , cancer research , medicine , apoptosis , in vitro , dentistry , gene , biochemistry
Aim Periodontitis induced by oral pathogens leads to severe periodontal tissue damage and osteoclast‐mediated bone resorption caused by inflammation. On the basis of 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 RNA i 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.