Disturbances of tooth form and eruption in the microphthalmic (mi) mouse: a light and electron microscopic study

Changes in the surrounding alveolar bone occur during tooth eruption. The microphthalmic (mi/mi) mouse suffers from osteopetrosis and lack of bone resorption; tooth form and eruption were examined in both affected mi/mi mice and unaffected litter-mates to determine the effect of osteopetrosis on tooth development and eruption. Paraffin sections of mandibles from 3, 7, 10, 13, 15 and 20-day-old mice were examined by light microscopy after staining with haematoxylin and eosin and for stable acid phosphatase activity. Mandibles from 15- and 20-day-old mice were examined by scanning electron microscopy. The ultrastructure of odontoblasts was observed in 15-day-old mice. Tooth eruption was significantly reduced in the mi/mi mice; the bone of affected mice increased in area with increasing age and marrow spaces narrowed. There was little bony remodeling in the mi/mi mouse, as indicated by layers of reversal lines. This lack of bone resorption affected tooth eruption and root formation. No abnormalities were detected in odontoblasts, suggesting functional normality, but the wide predentine layer in the mi/mi mouse may indicate an alteration in dentine mineralization.     

Delayed tooth eruption and suppressed osteoclast number in the eruption pathway of heterozygous Runx2/Cbfa1 knockout mice

Genetic studies have recently identified a mutation of one allele of runt-related gene 2 (RUNX2/CBFA1) as the cause for an autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD), which is characterised by hypoplasia of the clavicles and calvariae and widened sutures and fontanelles. In addition, CCD is frequently affected with multiple supernumerary teeth and the impaction and delayed eruption of teeth, the causes of all these dental abnormalities are still unknown. To clarify the cellular mechanism of the delayed tooth eruption in CCD, the process of tooth eruption was examined in heterozygous Runx2/Cbfa1 (mouse homolog of RUNX2/CBFA1) knockout mice, known to mimic most of the bone abnormalities of CCD. The timing of the appearance of maxillary and mandibular teeth into the oral cavity was significantly delayed in heterozygous mutant mice compared with wild-type mice. From postnatal days 8 to 10, an active alveolar bone resorption and a marked increase of the osteoclast surfaces was observed in the eruption pathway of both genotypes, but this increase was significantly suppressed in the mutant mice. In contrast, the osteoclast surfaces did not show a significant difference between the two genotypes in the future cortical area of femora. These results suggest that haploinsufficiency of Runx2/Cbfa1 does not effect the femoral bone remodelling but is insufficient for the active alveolar bone resorption essential for the prompt timing of tooth eruption. These results also suggest the possibility that impaired recruitment of osteoclasts is one of the cellular mechanisms of delayed tooth eruption in CCD patients.     

Age and order of eruption of primary teeth in Spanish children

Abstract – A longitudinal study on primary tooth eruption was performed in 114 Spanish children in two Primary Care Centers over 3 yr. Data from periodic observations and data collected by previously instructed parents was studied. Ages of tooth eruption were calculated for both sexes. Comparison between the two sides of the jaws showed a nonsignificant tendency towards earlier left side eruption. Comparison between maxillary and mandibular showed a significant earlier mandibular eruption for central incisors and second molars and a significant earlier maxillary eruption for lateral incisors. Comparison between sexes showed a tendency towards earlier eruption in boys for all teeth, significant only for mandibular central incisors, maxillary and mandibular lateral incisors and mandibular canines. Order of tooth eruption and its most frequent changes were also studied. When these findings were compared to studies performed in other populations it was concluded that ages and order of primary tooth eruption in Spanish children are similar to those found in other populations.     

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.     

An autoradiographic study on the effect of epidermal growth factor on cell proliferation in erupting mouse incisors

Epidermal growth factor (EGF) is a small polypeptide that induces precocious eyelid opening and incisor eruption in newborn mice; it stimulates cell proliferation in various cell types in vitro and in vivo. EGF was injected twice daily into newborn mice (0.4 μg/g) and tritiated thymidine was injected subcutaneously 6 h before killing the mice. Longitudinal sections of the lower incisors showed significantly more thymidine-labelled mitoses in the pre-odontoblast and pre-ameloblast layers at the basal ends of incisors in EGF-treated mice than in control mice. Although these results indicate that the EGF-induced precocious tooth emergence is associated with a stimulation of cell proliferation in the root sheath, this tissue may not be the target for the actions of EGF. Earlier studies have shown that root growth is not a factor in the generation of the eruptive force and, as neither the pre-ameloblasts nor pre-odontoblasts express EGF-receptors, the stimulation of cell proliferation in the root-sheath region appears to be a result and not a cause of accelerated tooth eruption, i.e. the increase in root growth may meet the need to maintain the tooth positionally during the accelerated eruptive process.     

Delayed tooth replantation in rats: effect of systemic antibiotic therapy with amoxicillin and tetracycline

Systemic antibiotic therapy (SAT) has usually been recommended after tooth replantation, but its actual value has been questioned. As there are no reports in the literature about its influence on tooth replantation, the aim of this study was to evaluate the influence of systemic administration of antibiotics (amoxicillin and tetracycline) at the different phases of the repair process (7, 15, 30 days) in delayed rat tooth replantation. Ninety Wistar rats (Rattus norvegicus albinus) had their maxillary right incisors extracted and bench‐dried for 60 min. The dental papilla, enamel organ, pulp tissue, and root surface‐adhered periodontal ligament were removed, and the teeth were replanted. The animals received no antibiotics (n = 30) or were medicated systemically with amoxicillin (n = 30) and tetracycline (n = 30), and were euthanized after 7, 15, and 30 days. Regardless of the evaluation period, the acute inflammatory infiltrate was less intense and root resorption presented smaller extent and depth in the group treated with amoxicillin. The results suggest that SAT has a positive influence on the repair process in delayed tooth replantation and that amoxicillin is an excellent treatment option.     

Resorption of entire impacted maxillary primary canine by permanent successor

A Japanese girl aged 4Y3M was referred for retarded eruption of the maxillary right primary canine. Radiographic examinations revealed the tooth to be impacted along with a tooth-like radiopaque lesion, which was extirpated under general anesthesia and histopathologically diagnosed as odontoma. At age 8Y3M, the position of the impacted primary canine was not changed, though the patient and guardians did not desire further treatment. Surprisingly, the crown as well as the root of the impacted primary canine appeared to be resorbed by its permanent successor after four years.     

An Unusual Complex Odontoma

Odontoma, complex type is an agglomerate of all the dental tissues that are characterized by normal histodifferentiation but abnormal morphodifferentiation producing little or no resemblance to normal tooth form. They are usually asymptomatic but often associated with eruption disturbances. An interesting case of unusually large complex odontoma that was associated with pain and an impacted as well as missing molar is reported.     

Eruption of a severely displaced second permanent molar following surgical removal of an odontoma

The process of tooth eruption is very complex, and many of its factors remain unknown. Although radiographic features can provide clues into the eruptive potential of a tooth, underlying factors that affect tooth development and eruption are not as well defined, ranging from local disturbances to systemic disease. In addition, it is difficult to predict which teeth will require treatment and when the optimal time is to intervene. The purpose of this report is to illustrate the eruption potential of an impacted molar following the removal of a developing odontoma, despite its unfavorable position in the bone, complete root development, and orthodontic attachment loss.     

An Erupted Silent Tumour

Odontomas are the most common odontogenic tumors of the oral cavity which are nonaggressive, hamartomatous in nature consisting of enamel, dentin and cementum. They are called as composite because they contain more than one type of tissue. They are generally asymptomatic, hence recognised on routine radiologic examination. The compound odontoma is composed of multiple small tooth like structures, whereas the complex odontoma consists of a conglomerate mass of enamel and dentine, which bears no anatomical similarity to the tooth. The eruption and infection of odontoma are uncommon, only few cases of erupted complex odontoma are reported in the literature. We report a case of silent erupting complex odontoma.     

Observational study investigating tooth extraction and the shortened dental arch approach

The shortened dental arch (SDA) provides a cost‐effective dentition, considering the population is ageing and retaining teeth for longer. The aims were to observe the reasons and sites of tooth extraction and assess the functional dentition over 15 years in dental practice. Subjects were recruited who required permanent tooth extractions between 2000 and 2015. The reasons for extractions were chosen from twelve extraction codes. Data were also collected for demographics, tooth position, root treated teeth and functional pairs remaining. Patient‐centred factors on reasons for tooth extraction and comments on chewing ability and aesthetics following extractions were recorded. Nine hundred and fifty‐one teeth were extracted in 900 patients. The mean age was 60 years (SD 20, SE 7, 95% CI 46, 74). Reasons for extraction were periodontal disease (n = 361, 38%), periapical infection (n = 288, 34%) or tooth and tooth‐root fractures (15%). Extractions included 201 (21%) second molars, 179 (19%) first molars, 152 (16%) second premolars, 95 (10%) first incisors, 86 (9%) second incisors, 76 (8%) canines and 67 (7%) first premolars. Following extractions, median functional pairs were 12, interquartile range (IQR) 19–7. Individuals with ≥10 functional pairs including anterior teeth (60%, n = 571) had no complaints with chewing ability or aesthetics. They did not require additional prostheses. Periodontal disease and periapical infection were the main causes for the extraction. First and second molars followed by second premolars were the most commonly extracted teeth. This study supports the SDA in creating a cost effective, functional dentition in an aging population, provided remaining teeth and restorations are preserved/maintained, oral health is promoted, and anterior aesthetic tooth replacement is ensured.     

The role of cathepsin K in oral and maxillofacial disorders

Cathepsin K (CTSK) was thought to be a collagenase, specifically expressed by osteoclasts, and played an important role in bone resorption. However, more and more research found that CTSK was expressed in more extensive cells, tissues, and organs. It may not only participate in regulating human physiological activity, but also be closely related to a variety of disease. In this review, we highlight the relationship between CTSK and oral and maxillofacial disorders on the following three aspects: oral and maxillofacial abnormities in patients with pycnodysostosis caused by CTSK mutations, oral and maxillofacial abnormities in Ctsk^?/? mice, and the role of CTSK in oral and maxillofacial diseases, including periodontitis, peri‐implantitis, tooth movement, oral and maxillofacial tumor, root resorption, and periapical disease.     

Comparative study of LHX8 expression between odontoma and dental tissue‐derived stem cells

J Oral Pathol Med (2011) 40 : 250–256 Background: LHX8 (LIM‐homeobox gene 8) is known as an important regulating factor in tooth morphogenesis. Odontoma is a mixed odontogenic tumor where epithelium and mesenchyme differentiated together, resulting in anomalous tooth structures. In this study, gene and protein expressions of LHX8 were analyzed in human odontoma‐derived mesenchymal cells (HODC) compared to adult dental mesenchymal stem cells (aDSC), as well as morphological and histological characteristics of odontoma were analyzed. Methods: aDSCs were isolated from normal teeth, and HODCs were isolated from surgically removed odontoma mass. Morphological and histological evaluations were performed to compare between compound odontomas and normal premolars. RT‐PCR and real‐time PCR were performed to identify LHX8 mRNA expression in the HODCs and aDSCs. LHX8 protein expression levels were observed by immunoblotting and immunofluorescent staining. Results: The compound odontoma was composed of multiple tooth‐like structures, which contained disorganized but recognizable enamel matrix, dentin, pulp, and cementum. LHX8 mRNA and LHX8 protein expressions were all higher in HODCs compared to those in aDSCs examined by RT‐PCR, immunoblot, and immunofluorescent staining. Especially, real‐time PCR showed 2.77‐fold higher LHX8 expression in HODCs than in normal periodontal ligament stem cells (PDLSCs), while alveolar bone marrow stem cells (ABMSCs) expressed 0.12‐fold LHX8 than PDLSCs. Conclusions: Based on these observations, LHX8 might play an important role in odontoma formation. This is the first report regarding the comparison of LHX8 expression between HODC and normal aDSCs and its overexpression in human samples. The specific mechanism of LHX8 in odontoma morphogenesis awaits further study.     

Tooth eruption and bone resorption: experimental investigation of the ia (osteopetrotic) rat as a model for studying their relationships

The osteopetrotic (ia) rat was examined as an experimental model for studying the dependence of tooth eruption on bone resorption. In ia rats eruption of incisors and first molars was rare and eruption of second and third molars was reduced and delayed. Autoradiographic studies of ³H-proline incorporation showed that delayed eruption was not due to reduced tooth formation. Microscopic study revealed distortion and failure of posterior growth of the apical ends of incisors, unresorbed bone blocking the eruption pathway for molars, and ankylosis of incisors and first molars to alveolar bone. A reduction in bone resorption, known to be the primary cause of the disease in ia rats, is presumed to be the cause of the delayed or unerupted dentition. The effectiveness of attempts to increase bone resorption in ia rats at an early age by injection of vitamin A and/or parathyroid extract or by parabiotic union with a normal littermate was determined by measuring their effect on the relative size of the tibial marrow cavity. Only parabiosis had a beneficial effect on bone resorption but surgical union could not be performed in animals young enough to affect eruption of incisors and first molars in ia parabionts. These results suggest that parabiotic union of neonatal rats should allow resorption to begin early enough to test the presumed dependence of tooth eruption on bone resorption.     

Comparative study of gene expression during tooth eruption and orthodontic tooth movement in mice

Objective:  The aim of this study was to understand tooth eruption by comparing the gene expression during tooth eruption and orthodontic tooth movement (OTM).
Materials and methods:  Orthodontic force was applied on maxillary molars for 2, 4, 7 and 14 days to study tooth movement. Mice at PN 0, 7, 10, 15 and 21 were fixed to observe tooth eruption. Comparative study of two procedures was assessed by haematoxylin and eosin, tartrate-resistant acid phosphatase staining and in situ hybridization for matrix metalloproteinase ( Mmp ) 2 , 13 , bone sialoprotein ( Bsp ) and osteocalcin ( Ocn ).
Results:  Tartrate-resistant acid phosphatase activity and expression of Mmp2 , 13 were obviously detectable in the compression region during OTM. They were also identified in the occlusal and apical region of alveolar bone during tooth eruption. Strong expression of Bsp and Ocn was detectable at the tension side during OTM. These genes were also expressed in the inner lateral region of alveolar bone adjacent to the tooth, but absent in the inner surface of the occlusal and root apical regions during tooth eruption.
Conclusion:  The process of alveolar bone metabolism during developmental eruption and OTM shares the same mechanism. Internal force, as the orthodontic force for OTM, may be initiating factor for tooth eruption.     

Retrospective analysis of factors influencing the eruption of delayed permanent incisors after supernumerary tooth removal.

AIM: This was to assess the predictability of eruption of delayed permanent incisors after supernumerary removal and creation of adequate space, in relation to: root maturity, degree of vertical impaction, and degree of angulation of impaction. METHODS: The dental records of children with supernumerary teeth delaying the eruption of permanent incisors were analysed. The type of a supernumerary tooth, its location and position were recorded, along with the stage of root maturation, angulation and vertical distance of impaction of the permanent incisor. At the initial surgery, the unerupted supernumerary tooth and any retained primary incisors were removed. The unerupted permanent incisor was not exposed. If necessary, the maxillary primary canines were removed to create sufficient space for eruption of the delayed permanent tooth. A secondary surgical procedure was planned after 18 months if there was no significant progress of the permanent tooth towards eruption. STATISTICS: All data were entered onto a Microsoft Excel spread sheet and analysed using Fisher's Exact Tests throughout due to the small numbers. RESULTS: Sixty-six supernumerary teeth were removed, 22 from boys and 44 from girls with ages ranging from 6 to 10 years 6 months at the time of surgery. Primary canines were extracted in 59.1% of cases. Spontaneous eruption occurred in 89.4% of delayed permanent teeth. The mean time to eruption was 9.2 months (median = 7 months). There was no statistically significant association between tooth eruption and root maturity or the degree of vertical impaction. There was an association between eruption and the degree of the angle of impaction of the permanent incisor (p<0.05). CONCLUSION: The majority of delayed permanent teeth erupt spontaneously if sufficient space is available or created at the time of removal of the unerupted supernumerary. The angulation of impaction of the permanent incisor is associated with a delay in eruption.     

Familial malignant osteopetrosis in children: a case report

The clinical, radiological, pathological and laboratory findings of two brothers with autosomal recessive malignant osteopetrosis are presented. Our findings are similar to characteristics previously reported in the literature about patients with osteopetrosis. The 6‐year‐old male patient was pale and had petechiae on his arms and legs. He also had macrocephalia, splenomegaly, severe pancytopenia, genu valgus, hypocalcemia, amaurosis, cessation of physical development, generalized bone sclerosis and recurrent infections with a history of multiple incidences of acute otitis media. Generalized bone sclerosis and irregular sclerosis of the maxilla and mandible were seen on radiographs. The oral mucosa was apparently normal but permanent tooth eruption was delayed although there was early loss of deciduous teeth. The recommended treatment was blood transfusion and therapy with antibiotics when necessary; a bone marrow transplant was not possible due to lack of a compatible donor.     

Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth

Sakuraba H, Fujiwara N, Sasaki‐Oikawa A, Sakano M, Tabata Y, Otsu K, Ishizeki K, Harada H. Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth. J Periodont Res 2012; 47: 81–88. © 2011 John Wiley & Sons A/S Background and Objective: It is well known that tooth root formation is initiated by the development of Hertwig’s epithelial root sheath (HERS). However, relatively little is known about the regulatory mechanisms involved in root development. As hepatocyte growth factor (HGF) is one of the mediators of epithelial–mesenchymal interactions in rodent tooth, the objective of this study was to examine the effects of HGF on the root development of mouse molars. Material and Methods: The HERS of mouse molars and HERS01a, a cell line originated from HERS, were used in this study. For detection of HGF receptors in vivo and in vitro, we used immunochemical procedures. Root development was assessed by implanting molar tooth germs along with HGF‐soaked beads into kidney capsules, by counting cell numbers in HERS01a cell cultures and by performing a 5′‐bromo‐2′‐deoxyuridine (BrdU) assay in an organ‐culture system. Results: HGF receptors were expressed in the enamel epithelium of molar germs as well as in HERS cells. HGF stimulated root development in the transplanted tooth germs, the proliferation of HERS01a cells in culture and HERS elongation in the organ‐culture system. Examination using BrdU revealed that cell proliferation in HERS was increased by treatment with HGF, especially that in the outer layer of HERS. This effect was down‐regulated when antibody against HGF receptor was present in the culture medium. Conclusion: Our results raise the possibility that HGF signaling controls root formation via the development of HERS. This study is the first to show that HGF is one of the stimulators of root development.