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Expression of extracellular matrix molecules, MMPs and TIMPs in alveolar bone, cementum and periodontal ligaments during rat tooth eruption.

Tooth eruption involves extensive degradation and reorganization of extracellular matrix (ECM) components. It is not known how ECM-degrading enzymes are coordinated with each other or how they are regulated in the event. The present study was designed to investigate mRNA expression of inhibitors of metalloproteinases (TIMPs) in comparison with matrix metalloproteinases (MMPs) as well as ECM molecules during rat first molar eruption using in situ hybridization. We also examined how TIMPs are involved in the process of tooth eruption, root formation, cementogenesis and alveolar bone remodelling. Expressions of type-I collagen, osteocalcin, MMPs 2 and 8, and TIMPs 1, 2 and 3 were shown in osteoblasts, osteocytes, cementoblasts, cementocytes and periodontal ligament fibroblasts, and the concomitant high expressions of the ECM molecules, MMPs and TIMPs in alveolar bone, cementum and periodontal ligaments were identified in the middle of first molar eruption. The remodelling of ECM in these periodontal tissues might be regulated through balance among the production of ECM molecules, the degradation of ECM by MMPs and the inhibition of MMPs by TIMPs during tooth eruption.

Alveolar Process↗

Secretion of CSF-1 and its inhibition in rat dental follicle cells: implications for tooth eruption.

Tooth eruption requires the presence of a dental follicle around the unerupted tooth. Before the onset of eruption there is an influx of mononuclear cells into the follicle which, in turn, form osteoclasts that erode the alveolar bone. Eruption can be accelerated by the injection of colony-stimulating factor-one (CSF-1), a molecule that is maximally transcribed and translated in the dental follicle cells at the time of peak influx of mononuclear cells into the follicle of the rat first mandibular molar. To determine if the rat dental follicle cells secrete the CSF-1 needed for these cellular events, conditioned medium was collected from cultures of these cells. Using as a bioassay, a cell line (m-NFS 60) that is responsive to CSF-1 for growth, it was shown that conditioned medium from the follicle cells stimulated growth of the m-NFS 60 cells by almost 33% over the controls. Western blots confirmed that CSF-1 was secreted into the medium. Treating the dental follicle cells with an antisense oligodeoxynucleotide probe against CSF-1 reduced the amount of CSF-1 produced. These results demonstrate that CSF-1 is secreted by the dental follicle cells and that the production of CSF-1 can be reduced with an antisense probe. This secretion by the dental follicle might recruit mononuclear cells into the follicle to initiate tooth eruption.

Alveolar Process↗

Cellular, molecular, and genetic determinants of tooth eruption.

Tooth eruption is a complex and tightly regulated process that involves cells of the tooth organ and the surrounding alveolus. Mononuclear cells (osteoclast precursors) must be recruited into the dental follicle prior to the onset of eruption. These cells, in turn, fuse to form osteoclasts that resorb alveolar bone, forming an eruption pathway for the tooth to exit its bony crypt. Some of the molecules possibly involved in the signaling cascades of eruption have been proposed in studies from null mice, osteopetrotic rodents, injections of putative eruption molecules, and cultured dental follicle cells. In particular, recruitment of the mononuclear cells to the follicle may require colony-stimulating factor-one (CSF-1) and/or monocyte chemotactic protein-1 (MCP-1). Osteoclastogenesis is needed for the bone resorption and may involve inhibition of osteoprotegerin transcription and synthesis in the follicle, as well as enhancement of receptor activator of NF kappa B ligand (RANKL), in the adjacent alveolar bone and/or in the follicle. Paracrine signaling by parathyroid-hormone-related protein and interleukin -1 alpha, produced in the stellate reticulum adjacent to the follicle, may also play a role in regulating eruption. Osteoblasts might also influence the process of eruption, the most important physiologic role likely being at the eruptive site, in the formation of osteoclasts through signaling via the RANKL/OPG pathway. Evidence thus far supports a role for an osteoblast-specific transcription factor, Cbfa1 (Runx2), in molecular events that regulate tooth eruption. Cbfa1 is also expressed at high levels by the dental follicle cells. This review concludes with a discussion of the several human conditions that result in a failure of or delay in tooth eruption.

Animals↗

Dynamic variations in the expression of type I collagen and its molecular chaperone Hsp47 in cells of the mouse dental follicle during tooth eruption.

Tooth eruption is a precisely timed and sequenced event that brings the tooth from within bone into a functional position in the mouth. Every part of the developing tooth has been theoretically implicated as a primary factor in this process, but it now appears that eruption is multifactorial, with the dental follicle and type I collagen playing an important part. Immunological probes were used here to investigate in vivo and in vitro the temporal and spatial expression of type I collagen and its molecular chaperone Hsp47 in the dental follicle during eruption. Mandibles were dissected from 2-, 5-, 9- and 11-day-old neonatal mice and fixed in 95% ethanol overnight. Sections of 7 microns were obtained and reacted with antibodies directed against type I collagen. Dental follicles were isolated from 2-, 5-, 9- and 11-day-old neonates and cells were grown in culture for 8 days. Slides were then reacted with antibodies directed against type I collagen and Hsp47. The production of type I collagen and Hsp47 in the follicle varied with the stage of dental development and eruption. There was a progressive decrease of type I collagen in the coronal part of the follicle, leading to an arrest of its production in these areas. These findings support the notion that cells of the coronal portion of the dental follicle stop producing type I collagen as a prerequisite to the initiation of tooth eruption and that this phenotype persists in vitro.

Animals↗

Current concepts of the biology of tooth eruption.

Tooth eruption is defined as the movement of a tooth from its site of development within the jaws to its position of function within the oral cavity. We present a critical review of evidence for the mechanisms and regulation of the intraosseous and supraosseous phases of eruption, with an emphasis upon the canine premolar model studied by the authors. Analyses at different stages of premolar eruption indicate that selective fragmentation of dental follicle protein DF-95 correlates with the presence of elevated levels of follicular collagenase and stromelysin, and with the onset of premolar movement. A dramatic decrease in these metalloproteinases followed initiation of movement. A biochemical and cell biological model for regulation of tooth eruption is proposed based upon these new and existing data.

Animals↗

The physiology of tooth eruption.

Tooth eruption is a complex phenomenon that involves numerous biologic activities of the bone and the soft tissue surrounding teeth. While the exact mechanisms of eruption are not clearly understood, numerous experiments of nature, including many of the inborn errors of metabolism, should prove useful in their study. Nutritional studies may also prove useful, but will always be problematic [56]. Studies on endocrinologic changes such as puberty, pregnancy, menopause, and diseases such as diabetes, have already shown that the periodontium may not be able to accommodate to changes in the body's equilibrium [51].

Animals↗

Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption.

Tooth eruption requires the presence of the dental follicle, a loose connective tissue sac that surrounds each unerupted tooth. Early postnatally in the rat, the follicle secretes colony-stimulating factor-1 (CSF-1) and monocyte chemotactic protein-1 (MCP-1), chemotactic molecules that are probably responsible for the recruitment of mononuclear cells. These cells, in turn, fuse to form osteoclasts, which are required for alveolar bone resorption to form an eruption pathway. Recent studies have shown that the osteoprotegerin (OPG) gene is expressed in the dental follicle, but in the first mandibular molar of the rat, that expression is reduced at day 3, the time of maximal osteoclast numbers on the alveolar bone. Inhibition of OPG expression at this time would allow osteoclast formation/activation. To determine if the dental follicle cells do secrete OPG that inhibits osteoclastogenesis, spleen cell cultures were established and soluble osteoclast differentiation factor (ODF) and CSF-1 added to some of them to promote osteoclast formation. In other cultures, dental follicle cells were added in an insert, such that they did not touch the spleen cells. Using a quantitative, tartrate-resistant acid phosphatase (TRAP) assay, it was shown that ODF and CSF-1 promoted osteoclastogenesis in the spleen cell cultures, but the addition of the follicle cells inhibited this and returned the TRAP activities to those seen in cultures of spleen cells only. Adding anti-OPG to these cultures, however, negated the effect of the follicle cells, demonstrating that OPG was the inhibitory molecule secreted by those cells. The follicle cells also immunostained for OPG, confirming that they synthesize OPG. These findings, coupled with those of other studies which show that the periodontal ligament (a derivative of the dental follicle) also secretes OPG, indicate that, except for the period of time in tooth eruption, where osteoclast formation is needed to form an eruption pathway, secretion of OPG would be the norm, presumably to prevent resorption of alveolar bone and subsequent disruption of the periodontal ligament.

Acid Phosphatase↗

Regional control by the dental follicle of alterations in alveolar bone metabolism during tooth eruption.

Tooth eruption is a localized, bilaterally symmetrical series of events which involves resorption and formation of alveolar bone on opposite sides of the tooth and requires the presence of the dental follicle. We examined the effect on eruption of selective surgical removal of parts of the follicle. Removal of either the basal or coronal halves of the follicle prevented eruption. Bone resorption and formation of an eruption pathway did not occur after removal of the coronal part of the follicle and bone formation did not occur after removal of the basal part of the follicle. Exposure and incisions of the follicle had no effect on eruption. We interpret these data to mean that the polarized resorption and formation of alveolar bone that occur around a tooth during eruption are regulated by the adjacent parts of the dental follicle.

Alveolar Process↗

The mechanism of tooth eruption.

Tooth eruption is an essential process for the survival of many different species and although the movement of teeth into function has been the subject of extensive research there is no consensus as to the mechanisms involved. Recent understanding of the mechanisms of cell activation and regulation has widened the scope for further research at the molecular level. This paper reviews the evidence for an eruptive force, its direction and source. The relationships between the eruptive force and molecular mechanisms of cell activation remain to be determined.

Alveolar Process↗

Ultrastructural features of the dental follicle associated with formation of the tooth eruption pathway in the dog.

The dental follicle is a loose connective tissue layer that surrounds the developing and erupting tooth. The follicle is necessary for tooth eruption in dogs and specific cellular changes occur in the follicle at the onset of tooth eruption. In particular, within the coronal region of the follicle next to areas of subsequent bone resorption there is an increase in mononuclear cells which have the ultrastructure features of monocytes and contain specific granules characteristic of preosteoclasts. The follicle has an extensive microvasculature and monocytes are often seen adjacent to capillaries and venules. Monocytes increase in number in direct proportion to the increase in osteoclasts that form the eruption pathway and decrease in number as soon as this activity is completed. It is postulated that monocytes enter the follicle from the microvasculature and then migrate to the walls of the bony crypt to participate in the formation of the eruption pathway.

Age Factors↗

[Maturation of enamel and tooth eruption].

The tertiary maturation of the erupting tooth needs much more time than it is supposed in literature. Possibly the completion is in accord with the decline of the caries activity at the end of the second decade of lifetime. With the aid of polarizing microscopy, electron microprobe, microhardness testing (Vickers) and scanning electron microscopy different stages of posteruptive maturation from human and other mammalian teeth were analysed. The mineralization level in the outer surface of human enamel is completing little by little in more than 5 years after eruption. This state is in the ruminant tooth obvious never within reach in consequence of the specific physiological conditions. The maturating mineralization after our preliminary findings is fundamentally different to remineralization.

Animals↗

The mechanisms and mediators of tooth eruption--models for developmental biologists.

Tooth eruption is a localized process in the jaws which exhibits precise timing and bilateral symmetry. It involves resorption and formation of bone on opposite sides of the erupting tooth and these activities depend on the dental follicle, a thin connective tissue investment of the developing and erupting tooth. Biochemical studies have shown that during eruption cells, proteins and enzymes change in the dental follicle and several growth factors and proteins known to accelerate or retard eruption have been identified. This review discusses these aspects of tooth eruption and proposes testable hypotheses and strategies that can make studies of tooth eruption new experimental opportunities for developmental biologists.

Animals↗

Bafilomycin A1 in bone resorption and tooth eruption in dogs.

Tooth eruption depends on bone resorption to form an eruption pathway. We have previously shown that a 2-wk local infusion of bafilomycin A1, an inhibitor of vacuolar H(+)-ATPases in osteoclasts, into the crypts of erupting mandibular premolars in dogs blocks bone resorption during this period and eruption of these teeth is delayed for 8 wk. Here we report the limits of inhibition of resorption that still permit eruption of these teeth. In 3 dogs 10(-6) M bafilomycin was delivered by osmotic minipumps early (18 wk) in eruption to the fourth premolar for 1, 3 or 4 wk. Radiographs taken at weekly intervals thereafter showed that bafilomycin delivery for 1 wk delayed eruption for 3 wk, delivery for 3 wk delayed eruption 9 wk and delivery for 4 wk prevented eruption. These data show that tooth eruption is delayed in direct proportion to the time resorption is blocked, and that this process for dog premolars cannot be blocked for more than 3 wk with 10(-6) M bafilomycin without blocking eruption itself.

Alveolar Process↗

The pattern and control of eruptive tooth movements.

Assumptions about eruptive tooth movements based on experience with adolescents may not be applicable to all ages. The eruptive process can be subdivided into six phases--three profunctional stages of individual tooth eruption (follicular growth, pre-emergent eruptive spurt, and postemergent eruptive spurt) and three postfunctional stages of the eruption of the entire dentition (juvenile occlusal equilibrium, circumpubertal occlusal eruptive spurt, and adult occlusal equilibrium). Differences in tooth-eruption rates in each of these phases result from variations in systemic and local factors. A series of working hypotheses which incorporate recent research into a theoretical explanation of the control of eruption during each stage is presented. Prior to emergence, the force of eruption may influence the rate of bone resorption and later of gingival remodeling, but the resorptive processes occur independently and are the rate-limiting factors in pre-emergent eruption. After emergence, intermittent occlusal loading disrupts the generative or adaptive mechanisms of the periodontal ligament so that eruption slows. The light continuous forces from resting tongue pressure also are significant influences on tooth eruption during periods of rapid facial growth. Cellular adaptation of the alveolar bone and gingiva plays an important role in the control of tooth eruption in the adult.

Adolescent↗

Nuclear matrix-intermediate filament proteins of the dental follicle/enamel epithelium and their changes during tooth eruption in dogs.

Tooth eruption activates a localized resorption and formation of alveolar bone and these activities depend upon the adjacent parts, coronal and basal, respectively, of the dental follicle-enamel epithelium. In this study the nuclear matrix-intermediate filament (NM-IF) proteins of these tissues were isolated in order to continue investigations into the molecular mechanisms underlying eruption. Dental follicles were removed from the third and fourth premolar of dogs at 13, 16 and 20 weeks (pre-, early, and mid-to-late eruption of these teeth) and NM-IF proteins were extracted from the coronal and basal halves. Most of the NM-IF protein profiles of these coronal and basal parts on one-dimensional, sodium dodecyl sulphate-polyacrylamide gel electrophoresis were remarkably constant, indicating an essentially uniform cellular composition. However, differences between these tissues were observed and some of these changed during eruption. Based on recent observations that nuclear matrix changes reflect and may even mediate cell-specific changes in gene expression, these findings suggest that changes in nuclear matrix proteins may be related to the molecular basis for some aspects of differential gene expression in the coronal and basal regions of the dental follicle and account for the ability of these tissues to activate bone resorption and formation during tooth eruption.

Alveolar Process↗