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Root apical complex, including Hertwig's epithelial root sheath, apical papilla, and dental follicle (DF), is the germinal center of root development, wherein the DF constantly develops into periodontal tissue. However, whether DF development is regulated by the adjacent apical papilla remains largely unknown. In this study, we employed a transwell coculture system and found that stem cells from the apical papilla (SCAPs) inhibit the differentiation and maintain the stemness of dental follicle stem cells (DFSCs). Meanwhile, partial SCAP differentiation markers were upregulated after DFSC coculture. High-throughput RNA sequencing revealed that the Hedgehog (Hh) pathway was significantly downregulated in DFSCs cocultured with SCAPs. Upregulation or downregulation of the Hh pathway can respectively activate or inhibit the multidirectional differentiation of DFSCs. Osteoglycin (OGN) (previously known as mimecan) is highly expressed in the dental papilla, similarly to Hh pathway factors. By secreting OGN, SCAP regulated the stemness and multidirectional differentiation of DFSCs via the OGN-Hh pathway. Finally, Ogn –/– mice were established using the CRISPR/Cas9 system. We found that the root length growth rate was accelerated during root development from PN0 to PN30 in Ogn –/– mice. Moreover, the hard tissues (including dentin and cementum) of the root in Ogn –/– mice were thicker than those in wild-type mice. These phenotypes were likely due to Hh pathway activation and the increased cell proliferation and differentiation in both the apical papilla and DF. The current work elucidates the molecular regulation of early periodontal tissue development, providing a theoretical basis for future research on tooth root biology and periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Collagen signaling is critical for proper bone and tooth formation. Discoidin domain receptor 2 (DDR2) is a collagen-activated tyrosine kinase receptor shown to be essential for skeletal development. Patients with loss of function mutations in DDR2 develop spondylo-meta-epiphyseal dysplasia (SMED), a rare, autosomal recessive disorder characterized by short stature, short limbs, and craniofacial anomalies. A similar phenotype was observed in Ddr2-deficient mice, which exhibit dwarfism and defective bone formation in the axial, appendicular, and cranial skeletons. However, it is not known if Ddr2 has a role in tooth formation. We first defined the expression pattern of Ddr2 during tooth formation using Ddr2-LacZ knock-in mice. Ddr2 expression was detected in the dental follicle/sac and dental papilla mesenchyme of developing teeth and in odontoblasts and the periodontal ligament (PDL) of adults. No LacZ staining was detected in wild-type littermates. This Ddr2 expression pattern suggests a potential role in the tooth and surrounding periodontium. To uncover the function of Ddr2, we used Ddr2slie/slie mice, which contain a spontaneous 150-kb deletion in the Ddr2 locus to produce an effective null. In comparison with wild-type littermates, Ddr2slie/slie mice displayed disproportional tooth size (decreased root/crown ratio), delayed tooth root development, widened PDL space, and interradicular alveolar bone defects. Ddr2slie/slie mice also had abnormal collagen content associated with upregulation of periostin levels within the PDL. The delayed root formation and periodontal abnormalities may be related to defects in RUNX2-dependent differentiation of odontoblasts and osteoblasts; RUNX2-S319-P was reduced in PDLs from Ddr2slie/slie mice, and deletion of Ddr2 in primary cell cultures from dental pulp and PDL inhibited differentiation of cells to odontoblasts or osteoblasts, respectively. Together, our studies demonstrate odontoblast- and PDL-specific expression of Ddr2 in mature and immature teeth, as well as indicate that DDR2 signaling is important for normal tooth formation and maintenance of the surrounding periodontium. [ABSTRACT FROM AUTHOR]

Tooth eruption is a unique biological process by which highly mineralized tissues emerge into the outer world, and it occurs concomitantly with tooth root formation. These 2 processes have been considered independent phenomena; however, recent studies support the theory that they are indeed intertwined. Dental mesenchymal progenitor cells in the dental follicle lie at the heart of the coupling of these 2 processes, providing a source for diverse mesenchymal cells that support formation of the highly functional tooth root and the periodontal attachment apparatus, while facilitating formation of osteoclasts. These cells are regulated by autocrine signaling by parathyroid hormone-related protein (PTHrP) and its parathyroid hormone/PTHrP receptor PPR. This PTHrP-PPR signaling appears to crosstalk with other signaling pathways and regulates proper cell fates of mesenchymal progenitor cell populations. Disruption of this autocrine PTHrP-PPR signaling in these cells leads to defective formation of the periodontal attachment apparatus, tooth root malformation, and failure of tooth eruption in molars, which essentially recapitulate primary failure of eruption in humans, a rare genetic disorder exclusively affecting tooth eruption. Diversity and distinct functionality of these mesenchymal progenitor cell populations that regulate tooth eruption and tooth root formation are beginning to be unraveled. [ABSTRACT FROM AUTHOR]

During organogenesis, the timing and patterning of dental pulp innervation require both chemoattractive and chemorepellent cues for precise spatiotemporal regulation. Our understanding of the signaling mechanisms that regulate tooth innervation during development, as well as the basic biology of these sensory neurons, remains rudimentary. In this study, we analyzed the expression and function of glial cell line-derived neurotrophic factor (GDNF) and its receptor tyrosine kinase, Ret, in the regulation of innervation of the mouse tooth pulp by dental pulpal afferent (DPA) neurons of the trigeminal ganglion (TG). Using reporter mouse models, we demonstrate that Ret is highly expressed by a subpopulation of DPA neurons projecting to the tooth pulp at both postnatal day 7 (P7) and in the adult. In the adult tooth, GDNF is highly expressed by many cell types throughout the dental pulp. Using a ubiquitous tamoxifen (TMX)-inducible Cre ( UBC-Cre/ERT2) line crossed to Ret conditional knockout mice ( Retfx/fx), Ret was deleted immediately prior to tooth innervation, and the neural projections into P7 molars were analyzed. TMX treatment was efficient in ablating >95% of Ret protein. We observed that UBC-Cre/ERT2; Retfx/fx mice had a significant reduction in the total number of neurites present within the pulp at P7, with a significant accumulation of aberrant fibers in the dental follicle and periodontium. In agreement with these findings, inhibition of Ret signaling through in vivo administration of a highly specific pharmacologic inhibitor (1NM-PP1) of Ret also caused a substantial reduction in pulpal innervation. Taken together, these findings indicate that Ret signaling regulates the timing and patterning of tooth innervation by dental primary afferent neurons of the TG during organogenesis and provide a rationale to explore whether alterations in the GDNF-Ret pathway contribute to pathophysiological conditions in the adult dentition. [ABSTRACT FROM AUTHOR]

Odontoameloblastomas (previously incorporated within ameloblastic odontomas) are matrix-producing odontogenic mixed tumors and are closely related in histologic appearance to the 2 other types of matrix-producing odontogenic mixed tumors: odontomas and ameloblastic fibro-odontomas. The presence or absence of intralesional, induced non-neoplastic tissue must be accounted for in the diagnosis. Herein we describe a naturally occurring odontoameloblastoma with extensive chondroid cementum deposition in a guinea pig (Cavia porcellus). Microscopically, the mass featured palisading neoplastic odontogenic epithelium closely apposed to ribbons and rings of a pink dental matrix (dentinoid), alongside extensive sheets and aggregates of chondroid cementum. The final diagnosis was an odontoameloblastoma given the abundance of odontogenic epithelium in association with dentinoid but a paucity of pulp ectomesenchyme. Chondroid cementum is an expected anatomical feature of cavies, and its presence within the odontoameloblastoma was interpreted as a response of the ectomesenchyme of the dental follicle to the described neoplasm. Our case illustrates the inductive capabilities of odontoameloblastomas while highlighting species-specific anatomy that has resulted in a histologic appearance unique to cavies and provides imaging and histologic data to aid diagnosis of these challenging lesions. [ABSTRACT FROM AUTHOR]

The dental follicle (DF), most often associated with unerupted teeth, is a condensation of ectomesenchymal cells that surrounds the tooth germ in early stages of tooth development. In the present study, we aim to isolate epithelial stem-like cells from the human DF and explore their potential differentiation into salivary gland (SG) cells. We demonstrated the expression of stem cell-related genes in the epithelial components of human DF tissues, and these epithelial progenitor cells could be isolated and ex vivo expanded in a reproducible manner. The human DF-derived epithelial cells possessed clonogenic and sphere-forming capabilities, as well as expressed a panel of epithelial stem cell-related genes, thus conferring stem cell properties (hDF-EpiSCs). When cultured under in vitro 3-dimensional induction conditions, hDF-EpiSCs were capable to differentiate into SG acinar and duct cells. Furthermore, transplantation of hDF-EpiSC-loaded native de-cellularized rat parotid gland scaffolds into the renal capsule of nude mice led to the differentiation of transplanted hDF-EpiSCs into salivary gland-like cells. These findings suggest that hDF-EpiSCs might be a promising source of epithelial stem cells for the development of stem cell-based therapy or bioengineering SG tissues to repair/regenerate SG dysfunction. [ABSTRACT FROM AUTHOR]

Aim. Odontogenic myxoma is a benign intraosseous neoplasm of the jaws, with a locally aggressive behavior and a high recurrence rate. CD-105 is a homodimeric cell membrane glycoprotein and is a component of the TGF-β1 growth factor receptor complex that modulates angiogenesis by regulating the proliferation, differentiation and cellular migration. The aim of this study is to quantify the microvascular density of the odontogenic myxoma based on the expression of CD-105. Materials and Methods. The analysis included 18 odontogenic myxoma and 18 dental follicles as controls. A standard immunohistochemical procedure was performed with the CD-105 antibody. Five representative fields (40×) of the odontogenic myxoma and the dental follicles were selected to determine the microvascular density, which was then followed by a descriptive and comparative statistical analysis. Results. Dental follicles presented a significantly higher microvascular density compared with odontogenic myxoma (P = .001). The odontogenic myxoma smaller than 3 cm showed a greater microvascular density than those larger than 3 cm in size (P > .05), and the microvascular density was lower in large odontogenic myxomas as compared with the dental follicles (P = .003). Conclusion. A weaker expression of CD-105 in odontogenic myxoma might indicate a lower angiogenic activity, suggesting that vascular proliferation has a limited role in the growth mechanisms and in the aggressive behavior of this neoplasm. [ABSTRACT FROM AUTHOR]

Cleidocranial dysplasia (CCD) is characterized by the runt-related transcription factor 2 (RUNX2) mutation, which results in delayed tooth eruption due to disturbed functions of dental follicle. Accumulating evidence has revealed a key regulatory circuit, including RUNX2, miR-31, and special AT-rich binding protein 2 (SATB2) acting in concert in mesenchymal stem cell homeostasis and functions. However, whether such a regulatory loop works in dental follicle cells (DFCs) remains unknown. Herein, we investigated the roles of RUNX2-miR-31-SATB2 in DFCs from patients with CCD (DFCs-CCD) to advance our understanding regarding physical tooth eruption. We identified a novel mutation on exon 5 (c.634T>G, p.T212P) in RUNX2 via exome sequencing in the CCD patient with typical clinical presentations. Compared with DFCs from healthy donors, DFCs-CCD displayed significantly lower osteogenic, osteoclast-inductive, and matrix-degrading capacities and had lower RUNX2 (a transcriptional inhibitor of miR-31), higher miR-31, and downregulated SATB2. Lower ratios of RANKL/OPG and RANKL/RANK, as well as decreased expression of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 2 (MMP2), would lead to inactivation of osteoclasts and suppression of bone matrix remodeling in DFCs- CCD. Furthermore, the roles of the RUNX2-miR-31-SATB2 loop in DFCs-CCD were revealed by endogenous miR-3I knockdown, which resulted in increased SATB2 and RUNX2, as well as osteoclast-inductive and matrix degradation capacities. Conversely, SATB2, RUNX2, MMP9, MMP2, and osteoclast-inductive factors expression declined upon ectopic miR-3I overexpression in normal DFCs. Importantly, neonatal mice with in vivo siRUNX2 delivery exhibited less activated osteoclasts around dental follicles and delayed tooth eruption. Together, these results suggest that RUNX2 mutation/haploinsufficiency disturbs osteoclast-inductive signaling in DFCs, which may be responsible for delayed tooth eruption in CCD patients. Manipulation of the RUNX2-miR-31-SATB2 loop may be a potential way to facilitate tooth eruption in CCD patients. [ABSTRACT FROM AUTHOR]

The tooth works as a functional unit with its surrounding bony socket, the alveolar bone. The growth of the tooth and alveolar bone is co-ordinated so that a studied distance always separates the 2, known as the tooth-bone interface (TBI). Lack of mineralization, a crucial feature of the TBI, creates the space for the developing tooth to grow and the soft tissues of the periodontium to develop. We have investigated the interactions between the tooth and its surrounding bone during development, focusing on the impact of the developing alveolar bone on the development of the mouse first molar (M1). During development, TRAP-positive osteoclasts are found to line the TBI as bone starts to be deposited around the tooth, removing the bone as the tooth expands. An enhancement of osteoclastogenesis through RANK-RANKL signaling results in an expansion of the TBI, showing that osteoclasts are essential for defining the size of this region. Isolation of the M1 from the surrounding mesenchyme and alveolar bone leads to an expansion of the tooth germ, driven by increased proliferation, indicating that, during normal development, the growth of the tooth germ is constrained by the surrounding tissues. [ABSTRACT FROM PUBLISHER]

Ectomesenchymal dental stem cells could be feasible tools for dental tissue engineering. Dental follicle cells are a promising example, since they are capable of differentiation into various dental tissue cells, such as osteoblasts or cementoblasts. However, cellular mechanisms of cell proliferation and differentiation are not understood in detail. Basic knowledge of these molecular processes may shorten the time before ectomesenchymal dental stem cells can be exploited for bone augmentation in regenerative medicine. Recent developments in proteomics and transcriptomics have made information about genome-wide expression profiles accessible, which can aid in clarifying molecular mechanisms of cells. This review describes the transcriptomes and proteomes of dental follicle cells before and after differentiation, and compares them with differentially expressed populations from dental tissue or bone marrow. [ABSTRACT FROM AUTHOR]

GoPro49 is a recently identified, novel Golgi protein that is expressed in embryonic mesenchymal tissues, including dental follicle. In the present study, we have tested the hypothesis that the gene is a specific marker for the dental follicle, and examined its expression during the development of mouse incisors and molars. In situ hybridization showed that GoPro49 is expressed in dental follicles from bud to post-eruption stages. The expression is intense throughout the dental follicle during crown development, and persists in the root follicle during root development. In the forming periodontal ligament, GoPro49 expression is down-regulated upon differentiation of the follicle cells to cementoblasts and osteoblasts marked by Bspl. In cultured dental follicle cells, the GoPro49 protein co-localizes with ß-COP, suggesting that GoPro49 may function in the secretory pathway. We conclude that GoPro49 is a novel, specific marker for the dental follicle and can be used to identify this tissue. Abbreviations: Bspl, bone sialoprotein 1; GoPro49, Golgi protein 49 kDa; El 6, embryonic day 16; HERS, Hertwig's epithelial root sheath; PDL, periodontal ligament; dpn. day post-natal.

The dental follicle (DF) differentiates into the periodontal ligament. In addition, it may be the precursor of other cells of the periodontium, including osteoblasts and cementoblasts. We hypothesized that stem cells may be present in the DF and be capable of differentiating into cells of the periodontium. Stem cells were identified in the DF of the rat first mandibular molar by Hoechst staining, alkaline phosphatase staining, and expression of side-population stem cell markers. These cells were shown to be able to differentiate into osteoblasts/cementoblasts, adipocytes, and neurons. Treating the DF cell population with doxorubicin, followed by incubation in an adipogenesis medium, suggested that the adipocytes originated from stem cells. Thus, a possibly puripotent stem cell population is present in the rat DF. [ABSTRACT FROM AUTHOR]

Teeth move through alveolar bone, whether through the normal process of tooth eruption or by strains generated by orthodontic appliances. Both eruption and orthodontics accomplish this feat through similar fundamental biological processes, osteoclastogenesis and osteogenesis, but there are differences that make their mechanisms unique. A better appreciation of the molecular and cellular events that regulate osteoclastogenesis and osteogenesis in eruption and orthodontics is not only central to our understanding of how these processes occur, but also is needed for ultimate development of the means to control them. Possible future studies in these areas are also discussed, with particular emphasis on translation of fundamental knowledge to improve dental treatments. [ABSTRACT FROM AUTHOR]

The dental follicle regulates the alveolar bone resorption needed for tooth eruption. In the rat first mandibular molar, a decrease in the expression of osteoprotegerin (OPG) in the dental follicle at day 3 enables the osteoclastogenesis needed for eruption to occur. Because colonystimulating factor-1 (CSF-1) is maximally expressed in the dental follicle at day 3, it was hypothesized that CSF-1 down-regulates OPG gene expression in the dental follicle in vivo. To test this, we compared the expression of OPG in osteopetrotic toothless (tl/tl) rats deficient in CSF- 1 with expression in their normal littermates for given ages. OPG gene expression was found to be higher in the dental follicle of the tl/tl mutants than in normals. Transfecting short interfering RNA specific for CSF-1 mRNA into dental follicle cells resulted in an up-regulation of OPG expression. Thus, these studies support our hypothesis that the down-regulation of OPG needed for tooth eruption is mediated by CSF-1. [ABSTRACT FROM AUTHOR]

Colony-stimulating factor-one (CSF-1) and parathyroid-hormone-related protein (PTHrP) down-regulate osteoprotegerin (OPG) gene expression in the dental follicle of the rat first mandibular molar. To examine this regulation at the signal transduction level, we treated cultured dental follicle cells with either phorbolmyristate acetate (PMA) or dibutyryl cyclic AMP (dbcAMP) to activate either protein kinase C (PKC) or protein kinase A (PKA). Our results demonstrate that PMA up-regulates OPG gene expression and down-regulates the expression of CSF-1 and the PTHrP receptor (PTHrP-R). Conversely, dbcAMP down-regulates OPG expression and up-regulates CSF-1 and PTHrP-R expression. Immunostaining shows that PMA also increases the steady-state levels of protein. Thus, treatment with agents that affect protein kinase activity also enhance the steady-state mRNA and protein levels of OPG, as well as decreasing the mRNA levels of CSF-1 and PTHrP-R. The PKC-a isoform may be critical in OPG regulation because PKC-a gene expression is enhanced by PMA and reduced by either CSF-1 or PTHrP. [ABSTRACT FROM AUTHOR]

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 NFkB ligand (RANKL), in the adjacent alveolar bone and/or in the follicle. Paracrine signaling by parathyroid-hormone-related protein and interleukin -1α, 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 (Run×2), 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. [ABSTRACT FROM AUTHOR]

A critical cellular event in tooth eruption is the formation of osteoclasts that are needed for bone resorption to form an eruption pathway. To analyze molecular regulation of osteoclast formation and activation, we examined the expression of osteoprotegerin (OPG), an inhibitor of osteoclast formation. In vivo, the gene expression of OPG is reduced in the dental follicle of the first mandibular molar of the rat at day 3 post-natally and in the mouse at day 5. This correlates with the days of maximal mononuclear cell influx and osteoclast numbers in the rat and mouse. Thus, inhibition of OPG gene expression on these days might allow osteoclasts to be formed and/or activated. In vitro studies demonstrated that both colony-stimulating factor-1 and parathyroid hormone-related protein reduced OPG gene expression in follicle cells, suggesting that these are candidate molecules for the in vivo inhibition of OPG expression. Osteoclast differentiation factor (ODF) immunolocalizes to the alveolar bone stromal cells adjacent to the follicle, whereby it might act to stimulate fusion of the mononuclear cells in the follicle. [ABSTRACT FROM AUTHOR]

The monocyte chemotactic protein-1 (MCP-1) gene is expressed in the dental follicle, a loose connective tissue sac that must be present for eruption to occur. The role of MCP-1 may be to recruit mononuclear cells (monocytes) to the dental follicle, where these cells, in turn, fuse to form osteoclasts to resorb alveolar bone for the formation of an eruption pathway. Thus, it was the aim of this study to determine if MCP-1 is secreted by dental follicle cells in culture and if its secretion is enhanced by potential tooth eruption molecules. Western blotting and a two-site capture enzyme-linked immunoabsorbent assay demonstrated that MCP-1 was synthesized and secreted into the medium by the follicle cells. Incubation of the cells with either transforming growth factor-beta one (TGF-(β1) or interleukin-one alpha (IL-lo) enhanced the secretion of MCP-1 by the cells. Measurement of the chemotactic ability of the conditioned medium to attract mouse monocytes demonstrated that the chemotaxis of the medium was increased if the cells had previously been incubated in IL-1α, although there appears to be a threshold concentration of MCP-1 above which chemotaxis is not enhanced. These combined results suggest that the critical initial cellular event of tooth eruption, an influx of mononuclear cells into the dental follicle at an early post-natal age, may be initiated by the secretion of MCP-1 by the dental follicle cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Colony-stimulating factor-i (CSF-1) accelerates tooth eruption in rats and is localized in the dental follicle, a loose connective tissue sac that is necessary for eruption to occur. CSF-1 enhances the cellular events that occur in the follicle prior to eruption-namely, an influx of monocytes into the follicle early post-natally to form the osteoclasts needed to resorb bone for the eruption pathway. Because CSF-1 levels are at a peak at day 3 post-natally, and because CSF-1 has an autocrine effect on its own gene expression, the question remains as to what causes the subsequent decline in CSF-1 protein and mRNA after day 3 post-natally. To determine if the autocrine effect is inhibited through the CSF-1 receptor, analysis of the CSF-1 receptor mRNA levels in cultured dental follicle cells reveals that high concentrations of CSF-1 reduce the gene expression of the CSF-1 receptor. Interleukin luc, a molecule that enhances CSF-1 gene expression, has no effect on CSF-1 receptor mRNA levels. Immunostaining for the CSF-1 receptor protein shows that it is present in the dental follicle early post-natally and is either absent or greatly reduced by day 10 post-natally. Earlier studies showed that the mRNA levels of the CSF-1 receptor also parallel this time course. Thus, the above results suggest that the feedback inhibition of the autocrine effect of CSF-1 on its own expression is through the effect of CSF-1 inhibiting the translation and transcription of its receptor. In turn, these molecular interactions possibly regulate the cellular events that occur in the follicle prior to and during eruption. [ABSTRACT FROM AUTHOR]

The dental follicle, a loose connective tissue sac which surrounds the unerupted tooth, is required for eruption to occur. Injection of colony-stimulating factor-1 (CSF-1) will accelerate molar eruption in rats, as well as stimulate tooth eruption in osteopetrotic rats. Utilizing in situ hybridization and reverse- transcription polymerase chain-reaction techniques, we show here that CSF-1 mRNA is present in vivo in the dental follicle of the first mandibular molar of the rat. Analysis of the molars from day 0 through day 10 post-natally demonstrates that the maximal expression of CSF-1 mRNA is at day 3 post-natally. Immunostaining also reveals that the CSF-1 mRNA is translated, with immunostaining for the CSF-1 itself, being heavy in early post-natal days and absent by day 9 post- natally. In view of the fact that there is a maximal influx of mononuclear cells (monocytes) into the dental follicle at day 3 post-natally-an influx which increases the numbers of osteoclasts needed to form a tooth eruption pathway--it is probable that the maximal expression of CSF-1 mRNA by day 3 post--natally contributes to this monocyte influx. Thus, this study establishes a relationship among a molecule (CSF-1), cell (monocyte), and tissue (dental follicle) that appear to play a major role in tooth eruption. [ABSTRACT FROM AUTHOR]

The article discusses the development of molecular biology and examines its effect on biomedical research, specifically with regards to tooth eruption. Details about the biology of tooth eruption and the causes of tooth eruption are provided. The role of molecules in bone resorption and the relationship between bone resorption and tooth eruption are explored. The role played by dental follicles and monocytes in tooth eruption is examined and the individual molecules which begin the tooth eruption process are also described.

Root development and tooth eruption are very important topics in dentistry. However, they remain among the less-studied and -understood subjects. Root development accompanies rapid tooth eruption, but roots are required for the movement of teeth into the oral cavity. It has been shown that the dental follicle and bone remodeling are essential for tooth eruption. So far, only limited genes have been associated with root formation and tooth eruption. This may be due to the difficulties in studying late stages of tooth development and tooth movement and the lack of good model systems. Transgenic mice with eruption problems and short or no roots can be used as a powerful model for further deciphering of the cellular, molecular, and genetic mechanisms underlying root formation and tooth eruption. Better understanding of these processes can provide hints on delivering more efficient dental therapies in the future. [ABSTRACT FROM PUBLISHER]