Experimental periodontitis in Msx2 mutant mice induces alveolar bone necrosis.

Abstract

Msx2 homeoprotein is a key transcription factor of dental and periodontal tissue formation and is involved in many molecular pathways controlling mineralized tissue homeostasis such as Wnt/sclerostin pathway. This study evaluated the effect of Msx2-null mutation during experimental periodontitis in mice. Experimental periodontitis was induced for 30 days in wild-type and Msx2 knock-in Swiss mice using Porphyromonas gingivalis infected ligatures. In knock-in mice, Msx2 gene was replaced by n-LacZ gene encoding β-galactosidase. Periodontal tissue response was assessed by histomorphometry, tartrate-resistant acid phosphatase histoenzymology, β-galactosidase, sclerostin immunochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling assay. Expression of Msx2 gene expression was also evaluated in human gingival biopsies using RT-qPCR. During experimental periodontitis, osteonecrosis area and osteoclast number were significantly elevated in knock-in mice compared with wild-type mice. Epithelial downgrowth and bone loss was similar. Sclerostin expression in osteocytes appeared to be reduced during periodontitis in knock-in mice. Msx2 expression was detected in healthy and inflamed human gingival tissues. These data indicated that Msx2 pathway influenced periodontal tissue response to experimental periodontitis and appeared to be a protective factor against alveolar bone osteonecrosis. As shown in other inflammatory processes such as atherothrombosis, genes initially characterized in early development could also play an important role in human periodontal pathogenesis.