Person: Martínez Álvarez, María Concepción
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First Name
María Concepción
Last Name
Martínez Álvarez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Odontología
Department
Area
Anatomía y Embriología Humana
Identifiers
8 results
Search Results
Now showing 1 - 8 of 8
Item Occurrence of cleft-palate and alteration of Tgf-β3 expression and the mechanisms leading to palatal fusion in mice following dietary folic-acid deficiency(Cells Tissues Organs, 2011) Maldonado Bautista, Estela; Murillo González, Jorge Alfonso; Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; Pérez De Miguelsanz, María Juliana; López Gordillo, Yamila; Partearroyo, Teresa; Paradas Lara, Irene; Maestro De Las Casas, María Del Carmen; Martínez Sanz, Elena; Varela Moreiras, Gregorio; Martínez Álvarez, María ConcepciónFolic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2–8 weeks’ induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks’ maternal FA deficiency caused complete CP in the fetuses although a 2 weeks’ maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor beta 3 (TGF-β3) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β3 null mutant mice, we investigated the presence of TGF-beta 3 mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β3 expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β3 expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of Tgf-β3 to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous Tgf-β3 compensates this deficit in vitro.Item Craniofacial and three-dimensional palatal analysis in cleft lip and palate patients treated in Spain(Scientific Reports, 2022) Viñas Pinedo, María José; Galiotto Barba, Francesca; Berenguer, Beatriz; Lorca García, Concepción; Murillo González, Jorge Alfonso; Martínez Álvarez, María Concepción; Martínez Sanz, ElenaGrowth alterations have been described in patients operated on for oral clefts. The purpose of this work was to analyze the craniofacial and palate morphology and dimensions of young adults operated on for oral clefts in early childhood in Spain. Eighty-three patients from eight different hospitals were divided into four groups based on their type of cleft: cleft lip (CL, n = 6), unilateral cleft lip and palate (UCLP, n = 37), bilateral cleft lip and palate (BCLP, n = 16), and cleft palate only (CPO, n = 24). A control group was formed of 71 individuals. Three-dimensional (3D) digital models were obtained from all groups with an intraoral scanner, together with cephalometries and frontal, lateral, and submental facial photographs. Measurements were obtained and analyzed statistically. Our results showed craniofacial alterations in the BCLP, UCLP, and CPO groups with an influence on the palate, maxilla, and mandible and a direct impact on facial appearance. This effect was more severe in the BCLP group. Measurements in the CL group were similar to those in the control group. Cleft characteristics and cleft type seem to be the main determining factors of long-term craniofacial growth alterations in these patients. Prospective research is needed to clearly delineate the effects of different treatments on the craniofacial appearance of adult cleft patients.Item In Vitro Manipulation of Cleft Palate Connective Tissue: Setting the Bases of a Proposed New Treatment(Journal of Surgical Research, 2006) Resel, Eva; Martínez Sanz, Elena; González, Ignacio; Trinidad, Eva; Garcillán, Beatriz; Amorós, María; Alonso Bañuelos, Carmen; González Meli, Beatriz; Lagarón, Emilio; Murillo González, Jorge Alfonso; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; López, María; Martínez Álvarez, María ConcepciónBackground. Palatoplasty has the undesired side effect of impaired mid-facial growth. To avoid this problem, we propose an alternative to palatoplasty. We hypothesize that if BMP-2 is injected together with a carrier into the periosteum of the cleft palate borders, border volume will increase and connective tissue cells will be activated to produce extra bone. Once these borders supported by bone reach the midline, extraction of their covering epithelia with trypsin will permit adhesion of the underlying tissues. We investigated in vitro the ability of cleft palate connective tissue cells to produce extra bone in the presence of BMP-2 and the possibility of using trypsin to remove the epithelium covering the cleft palate borders without impairing the underlying tissues’ ability to adhere. Materials and methods. We used the cleft palate presented by tgf- 3 null mice and small fragments of human cleft palate mucoperiosteum as models. Immunolabeling BMP-2-treated or untreated cultures with TUNEL and anti-osteocalcin or PCNA antibodies was performed. The epithelium of the cleft palate borders was removed with a trypsin solution, and the deepithelialized tissues were cultured in apposition. Results. BMP-2 induces differentiation toward bone on cleft palate connective tissue cells without producing cell death or proliferation. Trypsin removal of the cleft palate margins’ epithelium does not impair the underlying tissues’ adhesion. Conclusion. It is possible to generate extra bone at the cleft palate margins and to chemically eliminate their covering epithelia without damaging the underlying tissues, which allows further investigation in vivo of this new approach for cleft palate closure.- Project number: 144
Item Elaboración de modelos anatómicos y embriológicos mediante la impresión 3D(2016) Arráez Aybar, Luis Alfonso; Barrio Asensio, María Del Carmen; Cabrera Parra, Walter; Cuadra Blanco, Crótida De La; Río Sevilla, Aurora Del; García Gómez, Susana; Herrera Lara, Manuel Eugenio; Maestro De Las Casas, María Del Carmen; Martínez Álvarez, María Concepción; Mérida Velasco, José Ramón; Murillo González, Jorge Alfonso; Naredo Sánchez, Esperanza; Quirós Terrón, Luis; Pérez De Miguelsanz, María JulianaLa impresión 3D es un enfoque innovador en la docencia anatómica que puede proporcionar a los alumnos un material didáctico casi idéntico a la pieza embalsamada mitigando muchas de las múltiples controversias existentes en torno a la Disección Item Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains(Differentiation, 2008) Martínez Sanz, Elena; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; Maldonado Bautista, Estela; Murillo González, Jorge Alfonso; Garcillán, B; Amorós, M; Fuerte, T; Fernández, A; Trinidad, E; Rabadán, MA; López, Y; Martínez Salmeán, María Luisa; Martínez Álvarez, María ConcepciónAlthough palatal shelf adhesion is a crucial event during palate development, little work has been carried out to determine which molecules are responsible for this process. Furthermore, whether altered palatal shelf adhesion causes the cleft palate presented by Tgf-b3 null mutant mice has not yet been clarified. Here, we study the presence/distribution of some extracellular matrix and cell adhesion molecules at the time of the contact of palatal shelves in both wild-type and Tgf-b3 null mutant palates of two strains of mice (C57/BL/6J(C57), and MF1) that develop cleft palates of different severity. We have performed immunohistochemistry with antibodies against collagens IV and IX, laminin, fibronectin, the a5- and b1-integrins, and ICAM-1; in situ hybridization with a Nectin-1 riboprobe; and palatal shelf cultures treated or untreated with TGF-b3 or neutralizing antibodies against fibronectin or the a5-integrin. Our results show the location of these molecules in the wild-type mouse medial edge epithelium (MEE) of both strains at the time of the contact of palatal shelves; the heavier (C57) and milder (MF1) alteration of their presence in the Tgf-b3 null mutants; the importance of TGF-b3 to restore their normal pattern of expression; and the crucial role of fibronectin and the a5-integrin in palatal shelf adhesion. We thus provide insight into the molecular bases of this important process and the cleft palate presented by Tgf-b3 null mutant mice.Item Interactions between TGF-β1 and TGF-β3 and their role in medial edge epithelium cell death and palatal fusion in vitro(Differentiation, 2008) Murillo González, Jorge Alfonso; Maldonado Bautista, Estela; Barrio Asensio, María Del Carmen; Río Sevilla, Aurora Del; López, Yamila; Martínez Sanz, Elena; González, Ignacio; Martín, Concepción; Casado, Inmaculada; Martínez Álvarez, María ConcepciónIn recent decades, studies have shown that both TGF-beta(1) and TGF-beta(3) play an important role in the induction of medial edge epithelium (MEE) cell death and palatal fusion. Many of these experiments involved the addition or blockage of one of these growth factors in wild-type (WT) mouse palate cultures, where both TGF-beta(1) and TGF-beta(3) are present. Few studies have addressed the existence of interactions between TGF-beta(1) and TGF-beta(3), which could modify their individual roles in MEE cell death during palatal fusion. We carried out several experiments to test this possibility, and to investigate how this could influence TGF-beta(1) and TGF-beta(3) actions on MEE cell death and palatal shelf fusion. We double-immunolabelled developing mouse palates with anti-TGF-beta(1) or anti-TGF-beta(3) antibodies and TUNEL, added rhTGF-beta(1) or rhTGF-beta(3) or blocked the TGF-beta(1) and TGF-beta(3) action at different concentrations to WT or Tgf-beta(3) null mutant palate cultures, performed in situ hybridizations with Tgf-beta(1) or Tgf-beta(3) riboprobes, and measured the presence of TUNEL-positive midline epithelial seam (MES) cells and MES disappearance (palatal shelf fusion) in the different in vitro conditions. By combining all these experiments, we demonstrate great interaction between TGF-beta(1) and TGF-beta(3) in the developing palate and confirm that TGF-beta(3) has a more active role in MES cell death than TGF-beta(1), although both are major inductors of MES disappearance. Finally, the co-localization of TGF-beta(1), but not TGF-beta(3), with TUNEL in the MES allows us to suggest a possible role for TGF-beta(1) in MES apoptotic clearance.Item Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice(Pediatric research, 2019) López Gordillo, Yamila; Maldonado Bautista, Estela; Nogales, Laura; Río Sevilla, Aurora Del; Barrio Asensio, María Del Carmen; Murillo González, Jorge Alfonso; Martínez Sanz, Elena; Paradas Lara, Irene; Alonso Revuelta, María Isabel; Partearroyo, Teresa; Martínez Álvarez, María ConcepciónBACKGROUND: Cleft palate (CP) constitutes the most frequently seen orofacial cleft and is often associated with low folate status. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis, repair, and methylation. Whether the administration of isolated folic acid (FA) supplements prevents the CP caused by genetic mutations is unknown, as is its effect on the mechanisms leading to palate fusion. METHODS: FA was administered to females from two different strains of transforming growth factor β3 heterozygous mice. Null mutant progeny of these mice exhibit CP in 100% of cases of varying severity. We measured cleft length, height of palatal shelf adhesion, and the number of proliferating mesenchymal cells. Immunohistochemistry was also carried for collagen IV, laminin, fibronectin, cytokeratin-17, and EGF. RESULTS: FA supplementation significantly reduced CP severity and improved palatal shelf adhesion in both strains both in vivo and in vitro. Medial edge epithelium proliferation increased, and its differentiation was normalized as indicated by the presence and disposition of collagen IV, laminin, fibronectin, and cytokeratin-17. CONCLUSIONS: A maternal FA supplementation reduces the CP appearance by improving the mechanisms leading to palatal shelf adhesion.Item Initial stages of development of the submandibular gland (human embryos at 5.5–8 weeks of development)(Journal of Anatomy, 2019) Quirós Terrón, Luis; Arráez Aybar, Luis Alfonso; Murillo González, Jorge Alfonso; Cuadra Blanco, Crótida De La; Martínez Álvarez, María Concepción; Sanz Casado, José Vicente; Mérida Velasco, José RamónThe aim of this study was to determine the main stages of submandibular salivary gland development during the embryonic period in humans. In addition, we studied submandibular salivary gland development in rats on embryonic days 14-16 and expression in the submandibular salivary gland region with the monoclonal antibody HNK-1. Serial sections from 25 human embryos with a greatest length ranging from 10 to 31 mm (Carnegie stages 16-23; weeks 5.5-8 of development) and Wistar rats of embryonic days (E) 14-16 were analysed with light microscopy. Five stages of submandibular salivary gland development were identified. The prospective stage (1), between weeks 5.5 and early week 6, is characterized by a thickening of the epithelium of the medial paralingual groove in the floor of the mouth corresponding to the primordium of the submandibular salivary gland parenchyma. At this stage, the primordium of the parasympathetic ganglion lies below the lingual nerve. The primordium of the submandibular salivary gland parenchyma is observed in rats on E14 in the medial paralingual groove with mesenchymal cells, underlying the lingual nerve. These cells are HNK-1-positive, corresponding to the primordium of the parasympathetic ganglion. The bud stage (2), at the end of week 6 in humans and on E15 in rats, is characterized by the proliferation and invagination of the epithelial condensation, surrounded by an important condensation of the mesenchyme. The pseudoglandular stage (3) at week 6.5 is characterized by the beginning of the formation of lobes in the condensed mesenchyme. The canalicular stage (4), between week 7 and 7.5, is characterized by the appearance of a lumen in the proximal part of the submandibular duct. The innervation stage (5) occurs during week 8, with the innervation of the submandibular and interlobular ducts. Nervous branches arriving from the parasympathetic ganglion innervate the glandular parenchyma. Numerous blood vessels are observed nearby. Our results suggest that submandibular salivary gland development requires interactions among epithelium, mesenchyme, parasympathetic ganglion and blood vessels.