Dental and periodontal phenotypes of Dlx2 overexpression in mice.

Distal-less homeobox 2 (Dlx2) is a member of the homeodomain family of transcription factors and is important for the development of cranial neural crest cells (CNCCs)­derived craniofacial tissues. Previous studies revealed that Dlx2 was expressed in the cementum and a targeted null mutation disrupted tooth development in mice. However, whether Dlx2 overexpression may impair in vivo tooth morphogenesis remains to be elucidated. The present study used a transgenic mouse model to specifically overexpress Dlx2 in neural crest cells in order to identify the dental phenotypes in mice by observation, micro­computed tomography and histological examination. The Dlx2­overexpressed mice exhibited tooth abnormalities including incisor cross­bite, shortened tooth roots, increased cementum deposition, periodontal ligament disorganization and osteoporotic alveolar bone. Therefore, Dlx2 overexpression may alter the alveolar bone, cementum and periodontal ligament (PDL) phenotypes in mice.

Stem cells, tissue engineering and periodontal regeneration.

The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

Interactions of the tooth and bone during development.

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.

Evidence for expansion-based temporal BMP4/NOGGIN interactions in specifying periodontium morphogenesis.

Dental follicle cells in the periodontium are known to have the ability to differentiate into fibroblasts, cementoblasts, and osteoblasts during mouse periodontal development. From embryonic day 14 (E14) to postnatal day 11 (PN11), histological observations showed dramatic alterations in the relative width of the periodontal ligament (PDL)-forming region between the alveolar bone-forming and tooth root-forming area. At PN2, the width of the PDL-forming region showed a minimum, but with a higher expression of NOGGIN and proliferation cell nuclear antigen than the other regions. At PN11, the relative width of the PDL-forming region had expanded. Transplantation of individual regions of the developing tooth germ under the kidney renal capsule showed that dental follicle cells at E14 possessed the potential to develop into mineralized tissue after 3 weeks. These results suggested that the recovery of PDL width at PN11 may have resulted from cell proliferation and molecular interactions between osteogenic factors and their antagonists, such as interactions between bone morphogenetic protein 4 (BMP4) and NOGGIN, simlilar to those observed in suture, limb, and somite formation. To confirm the molecular interaction between BMP4 and NOGGIN, NOGGIN-protein bead implantation onto cultures was employed in vitro. This study thus indicates that harmonious interactions between NOGGIN and BMP in PDL-forming cells, which show higher cell proliferation than neighboring cells, might be important for proper periodontium development.

Dental follicle progenitor cell heterogeneity in the developing mouse periodontium.

As a developmental precursor for diverse periodontal tissues, the dental follicle (DF) harbors great promise for periodontal tissue regeneration. However, development of optimal therapy awaits the answer to a key question that impinges on many issues in development-Do adult progenitor tissues form a homogeneous cell population that differentiates into target tissues when they arrive at the site, or they contain heterogeneous cell populations that are committed to specific fates? To address the homogeneity/heterogeneity question, we analyzed differentiation pathways and markers in several cloned DF cell lines. Our studies revealed that each of our cloned DF lines featured remarkably unique characteristics, indicative of a separate and distinct lineage. One line, DF1, was high in proliferative activity but did not display any mineralization behavior, suggesting that it might be related to a periodontal ligament-type lineage. DF2 was similar to DF1, but featured remarkably high alkaline phosphatase activity indicative of a highly undifferentiated state. DF3 matched the mineralization characteristics of a same stage alveolar bone line AB1 in terms of gene expression and von Kossa staining, indicating that DF3 might be of cementoblastic or alveolar bone osteoblastic lineage. To verify the multilineage potential of the DF for purposes of tissue engineering, a series of differentiation induction experiments was conducted. For identification purposes, characteristics of these heterogeneous follicular progenitor cells were compared with follicle components in tissue sections of the postnatal developing periodontium. The presence of heterogeneous cell populations in the DF mirrors individual developmental pathways in the formation of the dental integument. The profound cellular heterogeneity of the DF as an adult progenitor for tissue regeneration also suggests that heterogeneous cellular constituents might play as much of a role in tissue regeneration as the inducible characteristics of individual lineages might do.

The potential contributions of cell and molecular biology to periodontal tissue regeneration.

Periodontal disease results in the gradual loss of supporting periodontal tissues, and ultimately, the teeth. Although conventional periodontal therapy can arrest the progression of the disease and allow healing, the resulting tissue is unlike that of the normal, healthy periodontium. Cellular and molecular biologic techniques may facilitate our understanding of the regeneration of the periodontium. This review discusses recent findings in cellular and molecular biology relevant to the biology of periodontal tissue regeneration.

Algunas consideraciones con relación a la dimensión biológica del periodonto. Sinonimia: espesor biológico - espacio biológico / Some considerations related to the periodontium's biological dimension. Synonymy: biological thickness - biological space

En este artículo se realiza una recopilación sobre algunos aspectos del denominado espacio, espesor o dimensión biológica del periodonto, también denominado unión dentogingival, desde la formación y desarrollo, la participación de los tejidos embrionarios, ectodermo, mesodermo y endodermo y la subsecuente evolución de la cuarta capa embrionaria denominada ectomesénquima. El resultante gingival final, luego de la erupción del diente permanente desde el punto de vista clínico, radiográfico, histológico y quirúrgico, con el fin de reconocer los límites calcificados de esta dimensión y los componentes de tejido blando epitelial y conectivo, así como sus dimensiones clínicas e histológicas. Una recopilación de los factores que lo alteran tanto genéticos como adquiridos los cuales modifican sus dimensiones superficiales, creviculares y subcreviculares. Los métodos de reconocimiento clínico del espesor crevicular, profundidad sondeable, el daño que haya causado la patología nivel de unión, parámetros utilizados también en la evaluación del resultado de los diferentes procedimientos terapéuticos y también necesarios para establecer la evolución favorable o desfavorables de un caso en un período de tiempo. Se revisan someramente los aspectos patológicos asociados con la enfermedad periodontal inflamatoria de origen bacteriano (periodontitis), con relación a los daños causados en la superficie blanda, dura y la profundidad de la dimensión crevicular (bolsa periodontal). Por último se describen las diferentes opciones de resolución de la bolsa peridontal por: a) Regeneración (neoformación tejidos perdidos). b) Reparación (cicactrización) de la dimensión biológica, según los hallazgos de la investigación en animales y humanos al utilizar las diferentes técnicas descritas para el tratamiento de la bolsa periodontal

Formation of the periodontal attachment in developing rabbit permanent incisors.

Permanent incisors from fetal New Zealand white rabbits aged 25-30 days in utero and from 1-20 days postnatally were processed for light microscopy. Examination of longitudinal and cross-sections revealed that cementum deposition and fiber attachment first occurred at 27 days in utero. A tooth-to-bone course of principal fibers confined to lateral aspects of the teeth was observed in 29-day fetal incisors, whereas lingually the periodontal ligament remained undeveloped as late as 5 days postnatally. In 20-day postnatal incisors, the development of the functional periodontal ligament was complete as evidenced by the fiber arrangement on all aspects of the root-analogue tooth surface. This study shows that 25-26-day fetal rabbit permanent incisors represent the end of the follicular phase, whereas 27-day fetal to 20-day postnatal teeth demonstrate distinct histologic characteristics of initial, incomplete and complete periodontal fiber attachment.

Dental lamina develops even within the mouse diastema.

In embryos of albino mice of ICR strain, collected between days 13 and 15, the epithelial lining within the future upper maxillary diastema was studied using frontal histological sections stained with hematoxylin-eosin and PAS methods. In embryos harvested on the 12th hr of day 13 (stage 13/12), a continuous epithelial rudiment of dentition was found in the anterior extension of the epithelial anlage of the first upper molar, up to the level of the lower anterior margin of the primary choana. In this stage the rudiment acquired, in the most anterior region of the future diastema, an arrangement typical for the dental lamina. In its dorsal extension there was found a distinct tooth anlage at the transitory stage lamina bud, which further (at stage 13/24) disintegrated into several segments. Starting with the day 14 (stage 14/12), the epithelial rudiment of dentition within the future upper diastema began to regress. From the stage 14/24 on, the anlage persisted only in its posterior terminal part where it merged with the epithelial lamina extending anteriorly from the anlage of the first upper molar. The existence of the dentition rudiment within the future mouse diastema constitutes the ontogenetic evidence that the diastema originates only secondarily--by regression. In some mutant strains of mice (tabby, crooked, sleek), the regression appears incomplete. The odontogenic potency of mouse diastema tissues should be considered when interpreting the results of in vitro experiments investigating the odontogenic inductive tissue interactions in mouse.