Fibroblast growth factor-23 (FGF23) is a hormone that modulates circulating phosphate (Pi) levels by controlling Pi reabsorption from the kidneys. When FGF23 levels are deficient, as in tumoral calcinosis patients, hyperphosphatemia ensues. We show here in a murine model that Fgf23 ablation disrupted morphology and protein expression within the dentoalveolar complex. Ectopic matrix formation in pulp chambers, odontoblast layer disruption, narrowing of periodontal ligament space, and alteration of cementum structure were observed in histological and electron microscopy sections. Because serum Pi levels are dramatically elevated in Fgf23−−, we assayed for apoptosis and expression of members from the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, both of which are sensitive to elevated Pi in vitro. Unlike X-linked hypophosphatemic (Hyp) and wild-type (WT) specimens, numerous apoptotic osteocytes and osteoblasts were detected in Fgf23−/− specimens. Further, in comparison to Hyp and WT samples, decreased bone sialoprotein and elevated dentin matrix protein-1 protein levels were observed in cementum of Fgf23−/− mice. Additional dentin-associated proteins, such as dentin sialoprotein and dentin phosphoprotein, exhibited altered localization in both Fgf23−/− and Hyp samples. Based on these results, we propose that FGF23 and (Pi) homeostasis play a significant role in maintenance of the dentoalveolar complex.
Alveolar bone supports teeth during chewing through a ligamentous interface with tooth roots. Although tooth loads are presumed to direct the development and adaptation of these tissues, strain distribution in the alveolar bone at different stages of tooth eruption and periodontal development is unknown. This study investigates the biomechanical effects of tooth loading on developing alveolar bone as a tooth erupts into occlusion. Mandibular segments from miniature pigs, Sus scrofa, containing M 1 either erupting or in functional occlusion, were loaded in compression. Simultaneous recordings were made from rosette strain gages affixed to the lingual alveolar bone and the M 2 crypt. Overall, specimens with erupting M 1 's were more deformable than specimens with occluding M 1 's (mean stiffness of 246 vs. 944 Mpa, respectively, p=0.004). The major difference in alveolar strain between the two stages was in orientation. The vertically applied compressive loads were more directly reflected in the alveolar bone strains of erupting M 1 's, than those of occluding M 1 's, presumably because of the mediation of a more mature periodontal ligament (PDL) in the latter. The PDL interface between occluding teeth and alveolar bone is likely to stiffen the system, allowing transmission of occlusal loads. Alveolar strains may provide a stimulus for bone growth in the alveolar process and crest.
Objective This study investigated the role of occlusion in the development of biomechanical properties of alveolar bone in the miniature pig, Sus scrofa. The hypothesis tested was that the tissues supporting an occluding tooth would show greater stiffness and less strain than that of a non-occluding tooth. Design Maxillary teeth opposing the erupting lower first molar (M1) were extracted on one side. Occlusion developed on the contralateral side. Serially administered fluorochrome labels tracked bone mineralization apposition rate (MAR). A terminal experiment measured in vivo buccal alveolar bone strain on occluding and non-occluding sides during mastication. Ex vivo alveolar strains during occlusal loading were subsequently measured using a materials testing machine (MTS/Sintech). Whole specimen stiffness and principal strains were calculated. Results MAR tended to be higher on the extraction side during occlusion. In vivo buccal shear strains were higher in the alveolar bone of the occluding side vs. the extraction side (mean of 471με vs. 281με, respectively; p=0.04); however, ex vivo shear strains showed no significant differences between sides. Stiffness differed between extraction and occlusion side specimens, significantly so in the low load range (344 vs. 668MPa, respectively; p=0.04). Conclusions Greater in vivo shear strains may indicate more forceful chews on the occluding side, whereas the similarity in ex vivo bone strain magnitude suggests a similarity in alveolar bone structure and occlusal load transmission regardless of occlusal status. The big overall change in specimen stiffness that was observed was likely attributable to differences in the periodontal ligament rather than alveolar bone.
Objectives This study investigated the effects of growth and tooth loading on the structural adaptation of the developing alveolar bone adjacent to the tooth root as the tooth erupted into function. Growth and occlusal function were expected to lead to increased alveolar bone density. Meanwhile, the supporting alveolar bone was expected to develop a dominant trabecular orientation (anisotropy) only after occlusal loading. Design Minipigs with erupting and occluding mandibular first molars (M1’s) were used to study the effects of growth and occlusal function on developing alveolar bone structure through comparison of alveolar bone surrounding M1’s. A second minipig model with one side upper opponent teeth extracted prior to occlusal contact with the M1 was raised until the non-extraction side M1’s developed full occlusal contact. The comparisons between extraction and non-extraction side M1 alveolar bone were used to emphasize the impact of occlusal loading on alveolar bone structure. Specimens were scanned on a Scanco Medical μCT 20 at a 22μm voxel resolution for structural analysis. Results With growth and occlusal function a distinct alveolar bone proper tended to develop immediately adjacent to the tooth root. The cancellous bone had thicker but fewer and more separated trabeculae after growth or occlusal loading. On the other hand, occlusal function did not lead to increased alveolar structural anisotropy. Conclusion During tooth eruption, growth and masticatory loads effect structural change in alveolar bone. The impact of occlusal function on cancellous bone anisotropy may need a more extensive period of time to demonstrate.
SummaryThe development of alveolar bone adjacent to the tooth root during tooth eruption is not well understood. This study tested the hypothesis that predominantly woven bone forms adjacent to tooth roots during tooth eruption, but that this immature structure transitions to lamellar bone when the tooth comes into function. Additionally, bone resorption was predicted to play a key role in transitioning immature bone to more mature, load-bearing tissue. Miniature pigs were compared at two occlusal stages, 13 weeks (n=3), corresponding with the mucosal penetration stage of M 1 tooth eruption, and 23 weeks (n=3), corresponding with early occlusion of M 1 /M 1 . Bone samples for RNA extraction and qRT-PCR analysis were harvested from the diastema and adjacent to M 1 roots on one side. Following euthanasia, bone samples for hematoxylin and eosin and TRAP staining were harvested from these regions on the other side. In contrast to expectations, both erupting and functioning molars had reticular fibrolamellar structure in alveolar bone adjacent to M 1 . However, the woven bone matrix in older pigs was thicker and had denser primary osteons. Gene expression data and osteoclast cell counts showed a tendency for more bone resorptive activity near the molars than at distant sites, but no differences between eruptive stages. Thus, although resorption does occur, it is not a primary mechanism in the transition in alveolar bone from eruption to function. Incremental growth of existing woven bone and filling in of primary osteons within the mineralized scaffold generated the fortification necessary to support an erupted and functioning tooth.
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