Methods: Single and compound KO mouse models for Akp2, Ank, and Enpp1 were analyzed to determine the role of PPi in controlling cementogenesis. Periodontal development in KO vs. control mice was analyzed by microCT, histology, histomorphometry, and immunohistochemistry.
Results: Excess PPi during development (Akp2 KO) inhibited cementogenesis, while conversely, deficient PPi (Ank or Enpp1 KO) encouraged increased cementum apposition to more than 10-fold WT. Low PPi and increased cementum conditions were associated with increased cementoblast expression of osteopontin (OPN), dentin matrix protein-1 (DMP1), and ANK or NPP1, all reflecting occurrence of excess mineralization. Compound Akp2/Ank double KO (dKO) mice were prepared to determine effect on cementum when PPi levels were relatively normalized by ablation of both ANK and TNAP. Presence of cementum in dKO mice indicated that TNAP is not absolutely necessary for cementogenesis, but that PPi removal is likely critical. Regions of hypercementosis in the dKO (more than 5-fold WT) suggested reduced PPi from loss of ANK was not sufficiently corrected by removing TNAP. Increased OPN, DMP1, and NPP1 linked to increased dKO cementum showed that PPi tunes not only cementum thickness, but also matrix properties.
Conclusions: PPi is a central regulator of acellular cementum formation, and physiologic PPi levels are carefully balanced by TNAP, ANK, and NPP1 in order to properly direct cementogenesis. The sensitivity of cementum to PPi may provide an advantageous strategy for cementum regeneration via PPi modulation.
Keywords: Cementum, Extracellular matrix molecules, Mineralization, Periodontics and Root