Exposure to endocrine disruptors and alterations in mineralized tissues: a narrative review / Exposición a disruptores endocrinos y alteraciones en tejidos mineralizados: revisión narrativa

Background: Endocrine Disrupting Chemicals (EDCs) would cause alterations in organs/systems of exposed individuals or their progeny. Objetive: To identify and analyze the main published findings on the effects of exposure to EDCs on teeth, cartilage, and bone. Material and Methods: Two databases were analyzed: Medline and Web of Science. Only observational studies analyzing the effect of EDCs on mineralized tissues published since 2006 were included in the study. Results: 25 articles were selected, most of them involving EDCs pesticides, plasticizers, or personal care products, highlighting organochlorine compounds, bisphenols, phthalates, dioxins, parabens, and perfluoroalkyls. Thirty-six per cent of the studies reported an accumulation of EDCs in teeth or bones, while 64% reported alterations in their development or morphology, mainly at the bone level, primarily affecting their mineral density and size, as well as that of the bones of exposed individuals or their progeny. The type of effect observed was related to the EDCs analyzed, and it seemed to depend on variables such as age, sex, ethnicity/race, and even the metabolic status of the individuals in the different species analyzed. No evidence associated with effects on cartilage was found. Conclusion: EDCs in the environment, at work, or at home, under different exposure routes, are capable of accumulating in teeth and bone, particularly affecting the latter. It is necessary to study the effect of EDCs on mineralized tissues in agro-industrial areas, especially on teeth.

Antecedentes: Los Químicos Disruptores Endocrinos (EDCs) causarían alteraciones en órganos/sistemas de individuos expuestos, o su progenie. Objetivo: Identificar y analizar los principales hallazgos publicados sobre el efecto de la exposición a EDCs en dientes, cartílago y hueso. Material y Métodos: Se analizaron dos bases de datos: Medline y Web of Science, incluyendo solo estudios observacionales publicados desde el 2006, analizando el efecto de los EDCs sobre tejidos mineralizados. Resultados:25 artículos fueron seleccionados, siendo la mayoría de los EDCs pesticidas, plastificantes o productos de cuidado personal, destacando los compuestos Organo-clorados, Bisfenoles, Ftalatos, Dioxinas, Parabenos y los Perfluoroalquilos. Un 36% de los estudios reportaron un acúmulo de EDCs en dientes o huesos, mientras que un 64% informaron de alteraciones en su desarrollo o morfología, particularmente a nivel de huesos, afectando principalmente su densidad mineral y su tamaño, así como el de los individuos expuestos o su progenie. El tipo de efecto observado tuvo relación con el EDCs analizado, pareciendo depender de variables tales como edad, sexo, etnia/raza e incluso el estado metabólico de los individuos, en las diferentes especies analizadas. No se encontraron evidencias asociadas a efectos en el cartílago. Conclusión: Los EDCs en el medio ambiente, ámbito laboral o doméstico, bajo distintas rutas de exposición, son capaces de acumularse en diente y hueso, afectando particularmente a este último. Es necesario estudiar el efecto de los EDCs en los tejidos mineralizados en zonas agroindustriales, particularmente a nivel de dientes.

Justification for the use of CBCT in the evaluation of bone support in periodontal disease. / Justificación del uso de la tchc en la evaluación del soporte óseo en enfermedad periodontal

Periodontal disease signs are detected by clinical and radiographic examination. First choice radiographic examinations are conventional radiographies, which complement clinical information. However, radiographies may bring limited information because of structure superimposition, which occurs because of two-dimensional reproduction of three-dimensional structures. To overcome this, emerges the possibility to use cone-beam computed tomography. This produces images in all three-dimensions of space of periodontal bone support structures, usually with higher dose of ionizing radiation than conventional radiographies. Therefore, cone-beam computed tomography indication must be justified. The hierarchical model of diagnostic efficacy and practice guidelines support the indication of cone-beam computed tomography for periodontal bone support evaluation in patients with infrabony and furcation defects, also considering the utility in planning and control of regenerative surgical treatments. Literature recommends cone-beam computed tomography only when clinical and conventional radiographic evaluation does not provide necessary information for a correct diagnosis and treatment planning, so it is not indicated as a first choice imagining method.

Los signos de la enfermedad periodontal se pesquisan de manera clínica y radiográfica. Los exámenes imagenológicos de primera elección son las radiografías convencionales, y complementan la información clínica. Sin embargo, las radiografías pueden entregar información limitada, debido a la sobreproyección de estructuras, esto debido a la reproducción bidimensional de estructuras tridimensionales. Para superar esto, surge la posibilidad de usar la tomografía computarizada de haz cónico. Esta genera imágenes tridimensionales y en cualquier plano del espacio, de las estructuras de soporte óseo periodontal, aunque con dosis de radiación ionizante que suele ser mayor que las radiografías convencionales. Por lo tanto, la indicación de uso de tomografía computarizada de haz cónico debe ser justificada. El modelo jerárquico de eficacia diagnóstica y las guías clínicas respaldan la indicación de tomografía computarizada de haz cónico para evaluar el soporte óseo periodontal en pacientes con defectos intraóseos y de furca, además de mencionar la utilidad en planificación y control de procedimientos quirúrgicos regenerativos. La literatura recomienda indicar tomografía computarizada de haz cónico sólo cuando la evaluación clínica y radiográfica convencional no aportan la información necesaria para un correcto diagnóstico y planificación de tratamiento, por lo que como primera elección no es indicada.

Distribución gen fimA de Porphyromonas gingivalis en pacientes chilenos con periodontitis crónica / Distribution of fimA genotypes of Porphyromonas gingivalis in Chilean patients with chronic periodontitis

RESUMEN: Antecedentes: Gen fimA de Porphyromonas gingivalis es un importante factor de virulencia asociado al desarrollo y la progresión de periodontitis. Objetivo: Cuantificar los niveles de P. gingivalis y la prevalencia de genotipos fimA en pacientes chilenos con diferentes grados de severidad de periodontitis crónica. Metodología: Se analizaron 135 muestras subgingivales de 45 adultos (15 con leve, 15 con moderada y 15 con periodontitis severa) mediante qPCR para P. gingivalis y genotipos fimA (I-V and Ib). Resultados: Se detectó P. gingivalis en el 73,3% de los pacientes con periodontitis crónica (46,6%, 73,3% y 100% para las formas leve, moderada y severa, respectivamente). El gen fimA se detectó en el 66% de los sujetos positivos para P. gingivalis, siendo el fimA IV y I los genotipos más prevalentes. Además, se detectó fimA IV en el 75% y fimA I en el 62,5% de los casos severos y moderados de periodontitis, respectivamente. Los niveles aumentados de fimA IV se asociaron con periodontitis crónica severa. Conclusiones: Los resultados sugieren una alta prevalencia de P. gingivalis y de sus genotipos fimA IV y I en pacientes con periodontitis crónica. Además fimA IV fue asociado con formas más severas de periodontitis crónica en esta población chilena.

ABSTRACT: Background: Porphyromonas gingivalis fimA gene is a key virulence factor and has been associated with development and progression of periodontal diseases. Aim: To quantify the levels of P. gingivalis and the prevalence of fimA genotypes in Chilean patients with different severity of chronic periodontitis. Methodology: One hundred and thirty five subgingival samples from 45 adults (15 with slight, 15 with moderate and 15 with severe chronic periodontitis, respectively) were analyzed by qPCR for P. gingivalis and fimA genotypes (I-V and Ib). Results: P. gingivalis was detected in 73.3% of patients (46.6%, 73.3% and 100% of patients with slight, moderate and severe chronic periodontitis, respectively). The genotype fimA was detected in 66% of positive subjects for P. gingivalis, whereas fimA IV and I were the most prevalent genotypes. In addition, fimA IV was detected in 75% and fimA I in 62.5% of severe and moderate cases, respectively. Increased levels of fimA IV were associated with severe chronic periodontitis. Conclusions: These findings suggest that there is a high prevalence of P. gingivalis and its fimA IV and I genotypes in chronic periodontitis patients. Furthermore, fimA IV was associated with severe chronic periodontitis in this Chilean population.

Ameloblastin as a putative marker of specific bone compartments.

Ameloblastin (AMBN), a member of the enamel matrix protein family, has been recently identified as integral part of the skeleton beyond the enamel. However, the specific role of endogenous AMBN in bone tissue is not fully elucidated. This study aims at investigating mRNA expression of AMBN in wild-type mice in different bone sites from early embryonic to adult stages. AMBN mRNA expression started at pre-dental stages in mouse embryos (E10.5) in both head and body parts. Using laser capture microdissection on 3-day-old mice, we showed an unambiguous mRNA expression of AMBN in extra-dental tissue (mandible bone). Screening of AMBN mRNA expression in adult mice (15-week-old) revealed that mRNA expression of AMBN varied according to the bone site; a higher mRNA levels in mandibular and frontal bone compartments were observed when compared to tibia and occipital bones. These results strongly suggest that AMBN expression may be regulated in a site-specific manner and identify AMBN as a putative in vivo marker of the site-specific fingerprint of bone organs.

Tracking endogenous amelogenin and ameloblastin in vivo.

Research on enamel matrix proteins (EMPs) is centered on understanding their role in enamel biomineralization and their bioactivity for tissue engineering. While therapeutic application of EMPs has been widely documented, their expression and biological function in non-enamel tissues is unclear. Our first aim was to screen for amelogenin (AMELX) and ameloblastin (AMBN) gene expression in mandibular bones and soft tissues isolated from adult mice (15 weeks old). Using RT-PCR, we showed mRNA expression of AMELX and AMBN in mandibular alveolar and basal bones and, at low levels, in several soft tissues; eyes and ovaries were RNA-positive for AMELX and eyes, tongues and testicles for AMBN. Moreover, in mandibular tissues AMELX and AMBN mRNA levels varied according to two parameters: 1) ontogenic stage (decreasing with age), and 2) tissue-type (e.g. higher level in dental epithelial cells and alveolar bone when compared to basal bone and dental mesenchymal cells in 1 week old mice). In situ hybridization and immunohistodetection were performed in mandibular tissues using AMELX KO mice as controls. We identified AMELX-producing (RNA-positive) cells lining the adjacent alveolar bone and AMBN and AMELX proteins in the microenvironment surrounding EMPs-producing cells. Western blotting of proteins extracted by non-dissociative means revealed that AMELX and AMBN are not exclusive to mineralized matrix; they are present to some degree in a solubilized state in mandibular bone and presumably have some capacity to diffuse. Our data support the notion that AMELX and AMBN may function as growth factor-like molecules solubilized in the aqueous microenvironment. In jaws, they might play some role in bone physiology through autocrine/paracrine pathways, particularly during development and stress-induced remodeling.

Bone resorption control of tooth eruption and root morphogenesis: Involvement of the receptor activator of NF-κB (RANK).

Activation of the receptor activator of NF-κB (RANK) is a crucial step in osteoclastogenesis. Loss- and gain-of-function mutations in the Rank gene cause, respectively, osteopetrosis and several forms of extensive osteolysis. Tooth and alveolar bone alterations are associated with these pathologies but remain to be better characterized. The aim of the present study was to establish the tooth and alveolar bone phenotype of a transgenic mouse model of RANK over-expression in osteoclast precursors. Early tooth eruption and accelerated tooth root elongation were observed subsequent to an increase in osteoclast numbers surrounding the tooth. The final root length appeared not to be affected by RANK over-expression, but a significant reduction in root diameter occurred in both control and root-morphogenesis-defective Msx2 null mutant mice. These results indicate that root length is independent of the surrounding bone resorption activity. In contrast, root diameter is sensitive to the activity of alveolar bone osteoclasts. These data suggest that early eruption and thin root are phenotypic features that could be associated with extensive osteolytic pathologies.