Osteopontin regulates dentin and alveolar bone development and mineralization

The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDI, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock -out (Ank(-/-)) mice, featuring reduced PP,, rapid cementogenesis, and excessive acellular cementum. Using this approach, we identified the matrix protein osteopontin (Sppl/OPN) as an elevated factor of interest in Ank(-/-) mouse molar PDL We studied the role of OPN in dental and periodontal development and function. During tooth development in wild type (WT) mice, Spp1 mRNA was transiently expressed by cementoblasts and strongly by alveolar bone osteoblasts. Developmental analysis from 14 to 240 days postnatal (dpn) indicated normal histological structures in Spp1(-/-) comparable to WT control mice. Microcomputed tomography (micro-CT) analysis at 30 and 90 dpn revealed significantly increased volumes and tissue mineral densities of Sppl(-/-) mouse dentin and alveolar bone, while pulp and PDL volumes were decreased and tissue densities were increased. However, acellular cementum growth was unaltered in Sppl(-/-) mice. Quantitative PCR of periodontal-derived mRNA failed to identify potential local compensators influencing cementum in Spp1(-/-) vs. WT mice at 26 dpn. We genetically deleted Spp1 on the Ank(-/-) mouse background to determine whether increased Sppl/OPN was regulating periodontal tissues when the PDL space is challenged by hypercementosis in Ank(-/-) mice. AnICh Sppl(-/-) double deficient mice did not exhibit greater hypercementosis than that in Anic(-/-) mice. Based on these data, we conclude that OPN has a non-redundant role regulating formation and mineralization of dentin and bone, influences tissue properties of PDL and pulp, but does not control acellular cementum apposition. These findings may inform therapies targeted at controlling soft tissue calcification. (C) 2017 Elsevier Inc. All rights reserved.