Failure to process dentin sialophosphoprotein into fragments leads to periodontal defects in mice

Dentin sialophosphoprotein (DSPP) plays a vital role in dentinogenesis. Previously, we showed that, in addition to dentin, DSPP is also highly expressed in alveolar bone and cellular cementum, and plays a crucial role in maintaining periodontal integrity; Dspp‐deficient mice demonstrate severe periodontal defects, including alveolar bone loss, decreased cementum deposition, abnormal osteocyte morphology in the alveolar bone, and apical migration of periodontal ligament. Dentin sialophosphoprotein in dentin and bone is cleaved into NH₂‐terminal and COOH‐terminal fragments. Whilst our previous study showed that the proteolytic processing of DSPP is critical for dentinogenesis, it is unclear whether the post‐translational cleavage of DSPP also plays an essential role in maintaining a healthy periodontium. In this study, we analyzed the periodontal tissues from transgenic mice expressing the uncleavable full‐length DSPP in the Dspp knockout (Dspp‐KO) background (named ‘Dspp‐KO/D452A‐Tg mice’), in comparison with those from wild‐type mice, Dspp‐KO mice, and mice expressing the normal Dspp transgene in the Dspp‐KO background (designated ‘Dspp‐KO/normal‐Tg mice’). We found that transgenic expression of the normal DSPP fully rescued the periodontal defects of the Dspp‐KO mice, whereas this was not the case in Dspp‐KO/D452A‐Tg mice. These results indicate that proteolytic processing of DSPP is essential to periodontal integrity.