Loss of Dkk-1 in osteocytes prevents alveolar bone loss in mice subjected to experimental periodontitis

Introduction Periodontitis is an infect-inflammatory highly prevalent disease that results in loss of connective tissue and bone support and can progress to bone destruction, tooth mobility and finally, tooth loss. Persistent inflammation causes alveolar bone loss not only by stimulating osteoclast activity, but also by directly suppressing bone formation via increasing the expression of Dickkopf-1 (Dkk-1), an inhibitor of Wnt signaling. In this study, we tested the hypothesis that Dkk-1 is a main contributor to periodontitis-induced alveolar bone loss (ABL).

Methods We subjected 12-week-old male and female mice with a specific deletion of Dkk-1 in osteocytes (Dkk-1;Dmp1-Cre mice) to experimental periodontitis. Their age- and sex-matched Cre-negative littermates served as controls. Periodontitis was induced by ligature around the upper 2nd left molar, the contralateral side was used as control. Mice were killed after eleven days, and maxillae were removed for macroscopic, micro-CT, and histological analyses. Blood samples were collected for CTx and P1NP measurement by ELISA.

Results The data show that the deletion of Dkk-1 on osteocytes prevented bone loss compared to cre negative mice with periodontitis (control). Micro-CT analysis showed that the distance between cementum enamel junction and alveolar bone crest (CEJ-ABC) was significantly reduced (0.28 ± 0.01 µm) in transgenic mice compared to their littermate controls (0.33 ± 0.02 µm; p < 0.05). Furthermore, the histological analysis displayed a significant reduction in osteoclast number as well as an increase in osteoblast and osteocyte numbers when compared to control. There was no change of P1NP serum levels between the groups, however, a significant reduction of CTx serum levels was observed in Dkk-1;Dmp1-Cre mice (35.6 ± 3.3 ng/ml) compared to control (57.0 ± 4.4 ng/ml).

Discussion Dkk1 derived from osteocytes plays a crucial role on alveolar bone loss in periodontitis. Thus, blocking Dkk-1 may represent a promising therapeutic strategy to treat periodontitis-induced bone loss.

Keywords Dickkopf-1, Periodontitis, alveolar bone loss

Korrespondenzadresse Lennart Lösser, Uniklinik Dresden, Medizinische Klinik 3, Bone Lab, Krenkelstraße 12, 01309 Dresden, Deutschland,

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