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

Abstract— 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.     

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.     

Tooth eruption: evidence for the central role of the dental follicle

Abstract The roles of the gubernaculum dentis, root formation, tooth crown and dental follicle in pre-functional eruption of a mandibular premolar have been studied in nine beagle dogs by radiographic and histologic evaluations of the effects of surgical ablation or removal of these structures on tooth eruption. The dental follicle was the only one of these structures required for the coordinated enlargement of the eruption pathway and formation of bone in the base of the bony crypt, the radiographic and histologic hallmarks of tooth eruption. These data, together with the topographic relationships of the dental follicle to areas of localized bone resorption and formation, are interpreted to mean that the dental follicle may influence, if not coordinate, these processes in tooth eruption.     

牙囊在牙萌出的作用及其调控机制研究进展

牙齿的萌出是指牙齿从颌骨内向口腔移动,穿透颌骨与口腔黏膜,然后接触对颌牙达到功能位置的复杂过程,这一过程在时间和空间上均受到严格管控。牙囊是围绕在发育中牙胚周围的一层来源于外胚间充质的疏松结缔组织,它通过招募单核细胞以及调控骨吸收和骨形成在牙齿萌出过程中发挥关键作用。国内外学者对牙囊在牙齿萌出中的作用和机制研究甚多,现将研究进展作一综述。     

调控牙萌出的细胞及分子机制研究进展

牙萌出是指牙冠形成后向平面移动,穿过牙槽骨和口腔黏膜到达功能位置的一系列复杂生理过程。目前研究认为,牙萌出由牙槽骨、牙囊、破骨细胞、成骨细胞及多种细胞因子等共同调控,其中牙囊参与调控牙槽骨吸收与形成,是牙萌出的必要条件;同时,牙根形成及牙周韧带在牙齿持续萌出阶段发挥作用。牙萌出的具体调控机制尚不明确,本文就牙萌出过程中发挥调控作用的细胞及分子机制的研究现状作一综述。     

Dental follicle cell-conditioned medium enhances the formation of osteoclast-like multinucleated cells

An influx of mononuclear cells and the subsequent increase of osteoclasts around tooth germs suggests that the dental follicle (DF) regulates or influences bone resorption required for tooth eruption. In order to study the effects of DF cell products on osteoclast formation during tooth eruption, a conditioned medium (CM) was created in which DF cells were added to mouse bone marrow cultures. Tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated cells were formed in the presence of 10 nM 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The CM, dose-dependently, stimulated the formation of TRAP-positive cells in the presence of 1,25(OH)2D3 for 14 days culture. The number of these cells decreased due to degradation in the control culture. A semi-solid methylcellulose assay in the presence of CM showed little expression of colony-stimulating activity. These results suggest that the DF cells of a developing tooth produce factor(s) that enhance osteoclast formation and bone resorption necessary for tooth eruption.     

倾斜种植体联冠桥修复上颌后牙游离缺失伴骨量不足的临床研究

目的探讨倾斜种植体联冠桥修复上颌后牙游离缺失伴上颌窦底骨量不足患者的临床疗效。方法收集上颌后牙游离缺失2颗以上、上颌窦底剩余牙槽骨高度2～7mm的患者13例,术前X线片评估,并制作手术导板,导板引导下在上颌窦前后壁倾斜植入种植体,1.5～3.0个月后行上部结构联冠桥修复,负载后1、3、6、9、12、18、24个月定期复查。结果负载后24个月观察期内28颗种植体稳固,无一松动脱落,种植体周围牙龈组织健康,无探诊出血,数字全景片检查显示种植体周围未见骨低密度影,无上颌窦炎症影像,负载24个月时,种植体近、远中牙槽骨高度与刚植入时的差异无统计学意义（t=1.54,t=1.63,P〉0.05）。上部结构修复后除6例患者出现桥体处食物嵌塞但容易自行清除外,咀嚼功能恢复满意。结论采用倾斜种植体联冠桥可有效修复部分上颌窦底骨量不足患者的上颌后牙游离缺失,避免行上颌窦提升手术。     

Effects of antiresorptive medications on tooth root formation and tooth eruption in paediatric patients

Tooth eruption is a pivotal milestone for children's growth and development. This process involves with the formation of the tooth root, the periodontal ligament (PDL) and the alveolar bone, as the tooth crown penetrates the bone and gingiva to enter the oral cavity. This review aims to outline current knowledge of the adverse dental effects of antiresorptive medications. Recently, paediatric indications for antiresorptive medications, such as bisphosphonates (BPs), have emerged, and these agents are increasingly used in children and adolescents to cure pathological bone resorption associated with bone diseases and cancers. Since tooth eruption is accompanied by osteoclastic bone resorption, it is expected that the administration of antiresorptive medications during this period affects tooth development. Indeed, several articles studying human patient cohorts and animal models report the dental defects associated with the use of these antiresorptive medications. This review shows the summary of the possible factors related to tooth eruption and introduces the future research direction to understand the mechanisms underlying the dental defects caused by antiresorptive medications.     

Osteoclast diseases and dental abnormalities

Tooth eruption depends on the presence of osteoclasts to create an eruption pathway through the alveolar bone. In diseases where osteoclast formation, or function is reduced, such as the various types of osteopetrosis, tooth eruption is affected. Diseases in which osteoclast formation or activity is increased, such as familiar expansile osteolysis and Paget's disease, are associated with dental abnormalities such as root resorption and premature tooth loss. Less is known about the origin of the dental problems in these conditions as there are no rodent models of these diseases as yet. In this short review, the genes currently known to be mutated in human osteoclast diseases will be reviewed and, where known, the effect of osteoclast dysfunction on dental development described. It will focus on human conditions and only mention rodent disease where no clear data in the human are available.     

Expression of tumour necrosis factor-alpha in the rat dental follicle

Tooth eruption requires the presence of the dental follicle, a loose connective tissue sac that surrounds each unerupted tooth. The follicle appears to regulate many of the cellular and molecular events of eruption, including the formation of osteoclasts needed to resorb alveolar bone to form an eruption pathway. To that end, the expression of the tumour necrosis factor-alpha (TNF-alpha) gene was examined in the dental follicle as a possible regulator of osteoclastogenesis. TNF-alpha was expressed slightly in the dental follicle of the first mandibular molar of the rat beginning at day 3 postnatally, but maximal expression was seen at day 9, a time that correlates with a slight burst of osteoclast formation seen at day 10 postnatally. In vitro, TNF-alpha was not expressed constitutively in the follicle cells but incubating them with interleukin 1alpha resulted in a strong expression of TNF-alpha after only 0.5h. TNF-alpha itself enhanced monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) gene expression. It also slightly decreased the expression of osteoprotegerin after 3-h incubation but this returned to the control level at 6h. MCP-1 and VEGF could aid in recruiting mononuclear cells (osteoclast precursors) to the dental follicle. In addition to the potential role of TNF-alpha in tooth eruption, this study suggests that the periodontal ligament derived from the dental follicle might have the capacity to synthesize TNF-alpha, and thereby contribute to the destructive events of periodontitis.     

Forced eruption: principles in periodontics and restorative dentistry

Forced orthodontic eruption is based on an understanding of the normal dental unit. The relationships between tooth, attachment apparatus, gingival unit, and force and stress demand consideration when forced eruption is used to treat carious or traumatic destruction of clinical crowns, lateral root perforations, or isolated vertical periodontal defects. Factors that must be judged acceptable prior to the initiation of therapy are (1) esthetics, (2) clinical root length, (3) root proximity, (4) root morphology, (5) furcation location, (6) individual tooth position, (7) collective tooth position, and (8) the ability to restore teeth. A correct diagnosis is essential and must precede the choice of forced eruption as a clinical solution. Correctly chosen, force eruption allows the tooth to assist in the support of a multiunit restoration or maintain its individual integrity while contributing to esthetics, speech, and function.     

Expression of odontogenic ameloblast-associated protein in the dental follicle and its role in osteogenic differentiation of dental follicle stem cells

ObjectiveOdontogenic Ameloblast-Associated Protein (ODAM) is encoded by a secretory calcium-binding phosphoprotein cluster gene, which generally plays an important role for mineralization. Dental follicle (DF) is essential in regulating bone formation for tooth eruption. This study aims to reveal ODAM expression in the DFs of developing and erupting molars, and to determine the possible role of ODAM.DesignDFs were collected from human third molars and rat mandibular molars for gene expression assessment and for establishment of cell cultures. RT-PCR and western blot were conducted to determine ODAM expression. Over- or silencing expression of ODAM in the dental follicle stem cells (DFSCs) was done by transfecting the cells with ODAM plasmid or siRNA to evaluate ODAM effects on osteogenesis.ResultsRat DFs weakly expressed ODAM at early-postnatal days, but a chronological increment of ODAM expression from days 1 to 11 was observed. Differences in expression of ODAM were seen in the human DFs of different individuals. In vitro, ODAM was expressed in DFSCs, but almost no expression in DF-derived fibroblast-like cells. Forcing the DFSCs to overexpress ODAM accelerated osteogenesis, whereas continuously silencing the ODAM in the DFSCs reduced osteogenesis only at 2 weeks of osteogenic induction.ConclusionsODAM is differentially expressed in the DFs of different age molars. Its expression is coincident with the increased bone formation of tooth crypt during tooth eruption in rat DFs. Increase of ODAM expression may accelerate osteogenic differentiation of DFSCs. Thus, ODAM expression in the DF may regulate bone formation for timely tooth eruption.     

Radiographic and histological analysis of tooth eruption through calcium phosphate ceramics in the cat

The effect of implanting calcium phosphate ceramics (CPC) into metabolically active sites within kitten mandibles during permanent premolar tooth eruption was examined. Forty kittens, 3–4 months of age were used: the deciduous second and third mandibular premolars were extracted and their sockets implanted with autologous blood clot, autogenous cancellous marrow, and the calcium phosphate ceramics, non-porous beta-tricalcium phosphate or porous hydroxylapatite. Animals were killed at 1, 2, 3, 4 and 5 months after implantation and undemineralized sagittal sections were evaluated by light microscopy. Eighty percent of hydroxylapatite implanted mandibles showed delay in tooth eruption concurrent with distortion in crown development, and a dense cellular fibro-proliferative response within the follicle of unerupted teeth. This response occurred in only one specimen with tricalcium phosphate, whereas normal eruptive patterns and crown development were routinely noted. Both the tricalcium phosphate and hydroxylapatite were integrated into the surrounding alveolar bone without evidence of an inflammatory response. Thus hydroxylapatite initiated a dense cellular fibrous network within the dental follicle preventing formation of an eruptive pathway, delaying tooth eruption and causing crown deformation. This was rarely seen with tricalcium phosphate, and may be due to the resorbability of tricalcium phosphate when compared to hydroxylapatite. Hydroxylapatite should therefore be used with caution for implanting into areas containing unerupted teeth with a metabolically active dental follicle.     

Microradiographic aspects of the growing mandibular body during permanent premolar eruption in the dog

In order to explore the bony changes in the mandibular body during prefunctional intraosseous eruption of premolars, 18 dogs aged from 8 to 16 wk at the beginning of experimental period, were given two intraperitoneal injections of oxytetracycline (50 mg/kg and 35 mg/kg 2 wk later) and 2 wk later a final injection of Alizarin red S (70 mg/kg). Microradiographic and fluorescent light microscopy studies showed that changes of the alveolar bony crypt walls were influenced by the growing dental germs which they surrounded. The cervical volumetric reduction, which indicates the end of crown formation, induced the apposition of lamellar and then woven bone on the adjacent alveolar walls. Furthermore, with occlusal displacement of the dental crown, the space below the tooth was immediately filled with woven bone trabeculae and chondroid tissue. The same phenomenon was observed at the level of the alveolar base, when the speed of tooth eruption was greater than that of root growth. During premolar development, the changes in the dental germ produces accommodating changes in the adjacent alveolar bone walls, and mandibular transversal growth has the same characteristics as that of a growing diaphysis.     

Inhibition of tooth eruption through calcium-phosphate ceramic granules in the rat

This experiment investigated the reason for disturbances of tooth eruption through hydroxylapatite (HA) granules. HA granules of compact and porous structure were implanted in the pathway of erupting teeth in 14 five-day-old rats. The results demonstrate that the use of this material can result in tooth retention and malformed tooth crowns. Tooth crown malformation can be traced to the formation of ceramo-dentinous complexes which promote bacterial invasion of the pulp cavity, resulting in arrest of the tooth eruption process.     

Gene expression of potential tooth eruption molecules in the dental follicle of the mouse

Tooth eruption requires alveolar bone resorption and the presence of the dental follicle, a loose connective tissue sac that surrounds each tooth. This bone resorption involves the follicle in that mononuclear cells enter the follicle to form osteoclasts which resorb bone to form the eruption pathway. In the rat first mandibular molar, probable eruption genes, CSF-1, c-fos, NFkappaB and MCP-1, are expressed maximally in the dental follicle at day 3 postnatally. This correlates with the time of peak influx of mononuclear cells into the follicle. In the mouse, the first peak influx of mononuclear cells into the first mandibular molar is at day 5 postnatally, and this study demonstrates that all four of the above resorption molecules are maximally expressed at this time in the dental follicle. Thus, this work suggests that these molecules may play a role in the cellular events of eruption (mononuclear cell influx and osteoclast formation) in the mouse molar at day 5 postnatally just as they do at day 3 in the rat molar. These results provide a standard for future studies on eruption in the mouse molar and extends the number of species in which putative eruption molecules are expressed at a critical time of eruption.     

Intermediate bone grafting of alveolar clefts

During the five year period 1980 to 1985 bone grafting was performed in 37 cleft patients before the eruption of the canine tooth (group IBG) and in 30 patients after the eruption of the canine tooth (group SGB). The initial healing was more favourable in the IBG group. In 72.5% of the clefts oro-nasal fistulae were present preoperatively. In all cases the fistulae were successfully closed. In the IBG group with orthodontic closure of the gap in the dental arch the interdental bone height in the grafted area was more than 75% of normal bone height in all clefts. In group SBG this situation was found in only 66% of the bone-grafted areas. There seems to be a clear relation between the age or the developmental stage of the canine tooth on the one hand and the possibility of orthodontic closure of the gap in the dental arch and good interdental bone height on the other hand. This also leads to the suggestion that if bone grafting to the alveolar cleft is required the operation should be performed before the eruption of the canine tooth on the cleft side.     

Effects of bisphosphonates on tooth eruption in children with osteogenesis imperfecta

Bisphosphonates are currently used in the therapy of osteogenesis imperfecta (OI) to decrease the bone fragility observed in OI patients. Bisphosphonate therapy delays tooth eruption in rats. The aim of this study was to determine whether or not bisphosphonate therapy delays tooth eruption in children. The clinical emergence of teeth was observed and the calculated dental age and the number of delayed teeth were determined for 33 OI patients treated with bisphosphonates and for strictly gender- and age-matched controls. There were significant differences between bisphosphonate-treated patients and controls for calculated dental age and number of delayed teeth. Bisphosphonate therapy was associated with a mean delay of 1.67 yr in tooth eruption in children with OI.     

Effect of human bone morphogenetic protein 2 implant on tooth eruption in an experimental design

This study evaluated the influence of recombinant human bone morphogenetic protein 2 (rhBMP-2) on the development and eruption of the secondary dentition. Primary premolar tooth extraction sockets in 12 16-week-old felines were implanted with either rhBMP-2, in collagen sponge or with buffer/absorbable collagen sponge (ACS). Unoperated jaw quadrants served as controls. Experimental conditions were randomized between jaw quadrants in all animals. Two animals receiving rhBMP-2/ACS and buffer/ACS in two quadrants per implant were sacrificed at 4 weeks postsurgery. Ten animals receiving rhBMP-2/ACS (two quadrants), buffer/ACS implants (one quadrant), and one quadrant serving as an unoperated control were evaluated at 12 weeks postsurgery. Clinical assessments included healing, eruption patterns, and crown development. Radiographic assessments included tooth development, eruption patterns, and bone formation. Histological observations were also made from the 4-week animals. The secondary dentition remained unerupted at 4 weeks postsurgery. Histological analysis showed normal alveolar bone coronal to the erupting teeth in rhBMP-2/ACS-implanted quadrants. At 12 weeks postsurgery, all teeth were erupted without differences between quadrants. Clinically, the crowns of all teeth were normal. Radiographs suggested that teeth in rhBMP-2/ACS- and buffer/ACS-implanted jaw quadrants exhibited similar tooth development and eruption patterns as the normal control. The evidence from this study suggests that surgical implantation of rh-BMP-2/ACS in the pathway of the developing and erupting secondary dentition does not interfere with the normal development and eruption patterns of the teeth.