Osteopontin regulates dentin and alveolar bone development and mineralization

Abstract

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 PDL, 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 (Spp1/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 240days postnatal (dpn) indicated normal histological structures in Spp1 comparable to WT control mice. Microcomputed tomography (micro-CT) analysis at 30 and 90dpn revealed significantly increased volumes and tissue mineral densities of Spp1 mouse dentin and alveolar bone, while pulp and PDL volumes were decreased and tissue densities were increased. However, acellular cementum growth was unaltered in Spp1 mice. Quantitative PCR of periodontal-derived mRNA failed to identify potential local compensators influencing cementum in Spp1 vs. WT mice at 26dpn. We genetically deleted Spp1 on the Ank mouse background to determine whether increased Spp1/OPN was regulating periodontal tissues when the PDL space is challenged by hypercementosis in Ank mice. Ank; Spp1 double deficient mice did not exhibit greater hypercementosis than that in Ank 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.

Osteoblast differentiation during orthodontic tooth movement

“…As the rates of cell proliferation and mineralization were elevated compared to the control group at all time points, the process of osteoblast linage progression in response to an orthodontic force appears to be dynamic and cannot be divided into discreet periods of proliferation, maturation and mineralization . Our findings support the recently reported role of OP in regulating alveolar bone mineralization …”

Regulation of Osteosclerosis by Inoculated Cd133+ PC3 Cells in Bone‐marrow Microenvironmental Niches

“…These changes suggest that OPN upregulates osteoblastic differentiation and influences the extent of tissue mineralization. This is consistent with previous studies pointing to a role for increased OPN deposition in the pathologies underlying mineralization and bone metastasis of breast cancer cells . In addition, Runx2 and OSX (osteogenesis‐specific transcription factors) are expressed during osteoblastic differentiation of BMSCs .…”

“…This is consistent with previous studies pointing to a role for increased OPN deposition in the pathologies underlying mineralization and bone metastasis of breast cancer cells. (44,45) In addition, Runx2 and OSX (osteogenesis-specific transcription factors) are expressed during osteoblastic differentiation of BMSCs. (46,47) Runx2 is required for differentiation of mesenchymal cells into pre-osteoblasts.…”

Vacuolar protein sorting 4B regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells through the Wnt-β-catenin signalling pathway

“…ALP activation is an early marker of odontoblastic and mineralized-cell differentiation, whereby ALP can induce matrix deposition by generating pyrophosphate [26]. OPN is an extracellular protein that regulates both bone and tooth mineralization [27]. It should be noted that some studies have proved that inactivation of a single osteogenic differentiation gene can reduce cell differentiation and mineralization of the dental tissue.…”