Functional importance of osteopontin in regulating periodontal mineralization

Objectives: The periodontal attachment complex is essential for tooth function and includes the cementum, periodontal ligament (PDL), and alveolar bone. While cementum grows by apposition and alveolar bone remodels in response to loading, essential factors preventing inappropriate mineralization of the collagenous and alkaline phosphatase-rich PDL remain unidentified. Our aim in these studies was to identify factors regulating mineralization in the periodontium.
Methods: Employing mouse models, including progressive ankylosis knock-out (Ank^-/-), osteopontin knock-out (Spp^-/-), and tissue nonspecific alkaline phosphatase knock-out (Alpl^-/-) mice, we probed the regulation of mineralization using laser capture microdissection, proteomic analysis, histology, immunohistochemistry, radiography, and microcomputed tomography to study dentoalveolar tissues.
Results: As a screening approach, we used proteomic analysis on microdissected PDL from Ank^-/- mice to identify factors altered under pro-mineralizing conditions of rapid cementogenesis. Matrix protein osteopontin (OPN) was identified as a candidate of interest based on increased presence in the Ank^-/- PDL and known function as a mineralization inhibitor. Developmental analysis revealed OPN localization in cementum, bone, and PDL. However, Spp1^-/- mice at 14, 26, and 60 days postnatal (dpn) exhibited no significant differences from controls in cementum formation, PDL maintenance, or tissue mineral density of alveolar bone, despite reports of increased mineral content in long bones. Alpl^-/- mice feature increased OPN (in addition to inorganic pyrophosphate) and present severe skeletal and dental mineralization defects, including lack of acellular cementum. Ablation of Spp1 in Alpl^-/- mice did not correct the cementum defect, in contrast to partial normalization reported in the skeleton.
Conclusions: While functioning to regulate skeletal modeling/remodeling, OPN does not have a critical and non-redundant physiological role directing mineralization of the periodontium, and does not contribute to cementum defects in Alpl^-/- mice, a model for hypophosphatasia. OPN likely functions in combination with other factors regulating periodontal mineralization through direct and indirect mechanisms.