Artículos y presentaciones en Congresos

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  • Artículo
    Acceso Abierto
    Nanostructured fumarate copolymer-chitosan crosslinked scaffold: an in vitro osteochondrogenesis regeneration study
    (2018) Lastra, María Laura; Molinuevo, María Silvina; Blaszczyk Lezak, Iwona; Mijangos, Carmen; Cortizo, Ana María
    In the tissue engineering field, the design of the scaffold inspired on the natural occurring tissue is of vital importance. Ideally, the scaffold surface must promote cell growth and differentiation, while promote angiogenesis in the in vivo implant of the scaffold. On the other hand, the material selection must be biocompatible and the degradation times should meet tissue reparation times. In the present work, we developed a nanofibrous scaffold based on chitosan crosslinked with diisopropylfumarate-vinyl acetate copolymer using anodized aluminum oxide (AAO) templates. We have previously demonstrated its biocompatibility properties with low cytotoxicity and proper degradation times. Now, we extended our studies to demonstrate that it can be successfully nanostructured using the AAO templates methodology, obtaining a nanorod-like scaffold with a diameter comparable to those of collagen fibers of the bone matrix (170 and 300 nm). The nanorods obtained presented a very homogeneous pattern in diameter and length, and supports cell attachment and growth. We also found that both osteoblastic and chondroblastic matrix production were promoted on bone marrow progenitor cells and primary condrocytes growing on the scaffolds, respectively. In addition, the nanostructured scaffold presented no cytotoxicity as it was evaluated using a model of macrophages on culture.
  • Artículo
    Acceso Abierto
    Advanced glycation end products and strontium ranelate promote osteogenic differentiation of vascular smooth muscle cells in vitro: preventive role of vitamin D
    (2017) Molinuevo, María Silvina; Fernández, Juan Manuel; Cortizo, Ana María; McCarthy, Antonio Desmond; Schurman, León; Sedlinsky, Claudia
    Advanced glycation end products (AGE) have been demonstrated to induce the osteogenic transdifferentiation of vascular smooth muscle cells (VSMC). Strontium ranelate (SR) is an anti-osteoporotic agent that has both anti-catabolic and anabolic actions on bone tissue. However, in the last years SR has been associated with an increase of cardiovascular risk. We hypothesize that SR can increase the osteoblastic trans-differentiation of VSMC and the induction of extracellular calcifications, an effect that could be potentiated in the presence of AGE and inhibited by simultaneous administration of vitamin D. The present results of our in vitro experiments demonstrate that AGE and SR alone or in combination, stimulate L-type calcium channels, causing an increase in reactive oxygen species and activation of both ERK and NFkB, with the final effect of promoting the osteogenic shift of VSMC. Importantly, these in vitro effects of AGE and/or SR can be prevented by co-incubation with vitamin D.
  • Artículo
    Acceso Abierto
    Fumarate copolymer–chitosan cross-linked scaffold directed to osteochondrogenic tissue engineering
    (2016) Lastra, María Laura; Molinuevo, María Silvina; Cortizo, Ana María; Cortizo, María Susana
    Natural and synthetic cross-linked polymers allow the improvement of cytocompatibility and mechanical properties of the individual polymers. In osteochondral lesions of big size it will be required the use of scaffolds to repair the lesion. In this work a borax cross-linked scaffold based on fumarate-vinyl acetate copolymer and chitosan directed to osteochondrondral tissue engineering is developed. The cross-linked scaffolds and physical blends of the polymers are analyzed in based on their morphology, glass transition temperature, and mechanical properties. In addition, the stability, degradation behavior, and the swelling kinetics are studied. The results demonstrate that the borax cross-linked scaffold exhibits hydrogel behavior with appropriated mechanical properties for bone and cartilage tissue regeneration. Bone marrow progenitor cells and primary chondrocytes are used to demonstrate its osteo- and chondrogenic properties, respectively, assessing the osteoand chondroblastic growth and maturation, without evident signs of cytotoxicity as it is evaluated in an in vitro system.
  • Artículo
    Acceso Abierto
    Effects of fructose-induced metabolic syndrome on rat skeletal cells and tissue, and their responses to metformin treatment
    (2017) Felice, Juan Ignacio; Schurman, León; McCarthy, Antonio Desmond; Sedlinsky, Claudia; Aguirre, José Ignacio; Cortizo, Ana María
    Aims: Deleterious effects of metabolic syndrome (MS) on bone are still controversial. In this study we evaluated the effects of a fructose-induced MS, and/or an oral treatment with metformin on the osteogenic potential of bone marrow mesenchymal stromal cells (MSC), as well as on bone formation and architecture. Methods: 32 male 8 week-old Wistar rats were assigned to four groups: control (C), control plus oral metformin (CM), rats receiving 10% fructose in drinking water (FRD), and FRD plus metformin (FRDM). Samples were collected to measure blood parameters, and to perform pQCT analysis and static and dynamic histomorphometry. MSC were isolated to determine their osteogenic potential. Results: Metformin improved blood parameters in FRDM rats. pQCTand static and dynamic histomorphometry showed no significant differences in trabecular and cortical bone parameters among groups. FRD reduced TRAP expression and osteocyte density in trabecular bone and metformin only normalized osteocyte density. FRD decreased the osteogenic potential of MSC and metformin administration could revert some of these parameters. Conclusions: FRD-induced MS shows reduction in MSC osteogenic potential, in osteocyte density and in TRAP activity. Oral metformin treatment was able to prevent trabecular osteocyte loss and the reduction in extracellular mineralization induced by FRD-induced MS.
  • Artículo
    Acceso Abierto
    Tautomerizable β-ketonitrile copolymers for bone tissue engineering: studies of biocompatibility and cytotoxicity
    (2015) Lastra, María Laura; Molinuevo, María Silvina; Giussi, Juan M.; Allegretti, Patricia E.; Blaszczyk Lezak, Iwona; Mijangos, Carmen; Cortizo, María Susana
    β-Ketonitrile tautomeric copolymers have demonstrated tunable hydrophilicity/hydrophobicity properties according to surrounding environment, and mechanical properties similar to those of human bone tissue. Both characteristic properties make them promising candidates as biomaterials for bone tissue engineering. Based on this knowledge we have designed two scaffolds based on β-ketonitrile tautomeric copolymers which differ in chemical composition and surface morphology. Two of them were nanostructured, using an anodized aluminum oxide (AAO) template, and the other two obtained by solvent casting methodology. They were used to evaluate the effect of the composition and their structural modifications on the biocompatibility, cytotoxicity and degradation properties. Our results showed that the nanostructured scaffolds exhibited higher degradation rate by macrophages than casted scaffolds (6 and 2.5% of degradation for nanostructured and casted scaffolds, respectively), a degradation rate compatible with bone regeneration times. We also demonstrated that the β-ketonitrile tautomeric based scaffolds supported osteoblastic cell proliferation and differentiation without cytotoxic effects, suggesting that these biomaterials could be useful in the bone tissue engineering field.
  • Artículo
    Acceso Abierto
    Induction of topographical changes in poly-ε-caprolactone scaffolds for bone tissue engineering: biocompatibility and cytotoxicity evaluations
    (2015) Alfano, Ana Laura; Fernández, Juan Manuel
    Bone tissue engineering (BTE) uses principles from different fields, such as medicine, biochemistry and engineering, in order to restore or improve damaged tissue. Topographic changes of Poly- - caprolactone scaffolds (PCL) have been previously induced by exposure of the polymer to various concentrations of NaOH for different periods of time. However, lack of consistency between the treatment conditions used by different research groups has led to inconsistent results, with no clear conclusion arising regarding the benefits of these treatments. The aim of this study was to evaluate how different treatments (time-concentration) with NaOH could affect its biocompatibility for bone marrow stromal cells (BMSC) and its cytotoxicity towards RAW 264.7 macrophages of a PCL scaffold. We also analyzed the physicochemical and mechanical properties of the PCL films after different treatment. We have shown that treatment with for 2 hours with NaOH produced changes that affected the hydrophobicity and biocompatibility of the scaffold by increasing the proliferation and ALP activity in cells grown on them. Beside, 24 hours of treatment with NaOH produced significant decreased in mechanical properties resulting in a scaffold highly fragile and low biocompatibility compared to PCL. Therefore, treatment for 2 hours with NaOH can be used to increase the biocompatibility of PCL scaffolds.
  • Artículo
    Acceso Abierto
    Saxagliptin affects long-bone microarchitecture and decreases the osteogenic potential of bone marrow stromal cells
    (2014) Sbaraglini, María Laura; Molinuevo, María Silvina; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond
    Diabetes mellitus is associated with a decrease in bone quality and an increase in fracture incidence. Additionally, treatment with anti-diabetic drugs can either adversely or positively affect bone metabolism. In this study we evaluated: the effect of a 3-week oral treatment with saxagliptin on femoral microarchitecture in young male non-type-2-diabetic Sprague Dawley rats; and the in vitro effect of saxagliptin and/or fetal bovine serum (FBS), insulin or insulin-like growth factor-1 (IGF1), on the proliferation, differentiation (Runx2 and PPAR-gamma expression, type-1 collagen production, osteocalcin expression, mineralization) and extracellular-regulated kinase (ERK) activation, in bone marrow stromal cells (MSC) obtained from control (untreated) rats and in MC3T3E1 osteoblast-like cells. In vivo, oral saxagliptin treatment induced a significant decrease in the femoral osteocytic and osteoblastic density of metaphyseal trabecular bone and in the average height of the proximal cartilage growth plate; and an increase in osteoclastic tartrate-resistant acid phosphatase (TRAP) activity of the primary spongiosa. In vitro, saxagliptin inhibited FBS-, insulin- and IGF1-induced ERK phosphorylation and cell proliferation, in both MSC and MC3T3E1 preosteoblasts. In the absence of growth factors, saxagliptin had no effect on ERK activation or cell proliferation. In both MSC and MC3T3E1 cells, saxagliptin in the presence of FBS inhibited Runx2 and osteocalcin expression, type-1 collagen production and mineralization, while increasing PPAR-gamma expression. In conclusion, orally administered saxagliptin induced alterations in long-bone microarchitecture that could be related to its in vitro downregulation of the ERK signaling pathway for insulin and IGF1 in MSC, thus decreasing the osteogenic potential of these cells.
  • Artículo
    Acceso Abierto
    Insulin-deficient diabetes-induced bone microarchitecture alterations are associated with a decrease in the osteogenic potential of bone marrow progenitor cells: preventive effects of metformin
    (2013) Tolosa, María José; Chuguransky, Sara Rocío; Sedlinsky, Claudia; Schurman, León; McCarthy, Antonio Desmond; Molinuevo, María Silvina; Cortizo, Ana María
    Aims: Diabetes mellitus is associated with metabolic bone disease and increased lowimpact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved. Methods: Partially insulin-deficient diabetes was induced in rats by nicotinamide/streptozotocin- injection, with or without oral metformin treatment. Femoral metaphysis microarchitecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARg and receptor for advanced glycation endproducts (RAGE) were investigated. Results: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slight decrease in trabecular area and a significant reduction in osteocyte density, growth plate height and TRAP (tartrate-resistant acid phosphatase) activity in the primary spongiosa. BMPC obtained from diabetic animals showed a reduction in Runx-2/PPARg ratio and in their osteogenic potential, and an increase in RAGE expression. Metformin treatment prevented the diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential. Conclusion: Partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential, which could be mediated by a decrease in their Runx-2/PPARg ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
  • Artículo
    Acceso Abierto
    La diabetes altera el potencial osteogénico de células progenitoras de médula ósea: efectos del tratamiento con metformina
    (2012) Tolosa, M. J.; Chuguransky, S. R.; Schurman, León; Sedlinsky, Claudia; Cortizo, Ana María; McCarthy, Antonio Desmond; Molinuevo, María Silvina
    En este trabajo, estudiamos el efecto de una Diabetes inducida por destrucción parcial de la masa de células beta pancreáticas, sobre el compromiso osteogénico de células progenitoras de médula ósea (CPMO), y su modulación por el tratamiento oral con Metformina. Para ello utilizamos ratas Sprague Dawley, divididas en cuatro grupos: controles [C], controles tratadas con Metformina [M], diabéticas [D], y diabéticas tratadas con Metformina [DM]. La inducción de Diabetes se realizó, por inyección intraperitoneal sucesiva de ácido nicotínico y estreptozotocina. Sobre los cultivos de CPMO se evaluó la actividad específica de Fosfatasa Alcalina (FAL) y la producción de Colágeno tipo 1 (Col-1) en estado basal y en medio de diferenciación osteogénico luego de 15 días. A los 21 días, se evaluaron los depósitos de mineral extracelular. La FAL y el Col-1 de CPMO basales, no mostraron diferencias significativas entre los cuatro grupos experimentales. Al cabo de 15 días, las CPMO de ratas M mostraron un incremento en el Col-1 de 122 % respecto de C; D 30 % respecto de C y DM 68 % respecto de C. La FAL expresó un 171 % para M, 34 % para D; y 125 % para DM todos respecto de C. Luego de 21 días, se observó una disminución en la mineralización de las CPMO de D (65 % respecto del grupo C). El tratamiento con metformina incrementó la mineralización de las CPMO en todos los casos. En conclusión, en nuestro modelo experimental de Diabetes, ésta disminuye el potencial osteogénico de las CPMO, un efecto que es parcialmente revertido por el tratamiento oral con Metformina. Estos hallazgos podrían explicar, al menos en parte, las alteraciones óseas descriptas en el hueso asociadas con la Diabetes.
  • Artículo
    Acceso Abierto
    Universal versus selective screening for the detection, control and prognosis of gestational diabetes mellitus in Argentina
    (2009) McCarthy, Antonio Desmond; Curciarello, Renata; Castiglione, Nicolás; Fernández Tayeldín, Marina; Costa, Diego; Arnol, Verónica; Prospitti, Anabela; Aliano, Analía; Archuby, Daniela; Graieb, Augusto; Torres, María J.; Etcheverry, Susana B.; Apezteguia, María Cármen
    In all, 1,702 unselected pregnant women from the city of La Plata were tested for gestational diabetes mellitus (GDM) and evaluated to determine GDM prevalence and risk factors. In women with GDM, we evaluated compliance with guidelines for GDM management, and perinatal complications attributable to GDM. GDM prevalence was 5.8%, and its risk factors were pre-gestational obesity, previous hyperglycaemia, age[30 years, previous GDM (and its surrogate markers). In primi-gravida (PG) subjects, GDM was equally prevalent in the presence (4.2%) or absence (4.0%) of risk factors. In multi-gravida (MG) women, although risk factors doubled the prevalence of GDM (8.6%), in the absence of risk factors GDM prevalence was similar to that of PG women (3.9%). Half of all women with GDM received inadequate post-diagnosis obstetric control, and this induced a fourfold increase in infant perinatal complications. In conclusion, all nonhyperglycaemic 24–28-week pregnant women should be tested for GDM, although particular attention must be paid to MG women with risk factors.
  • Artículo
    Acceso Abierto
    Dilemas contemporáneos en torno a la construcción patrimonial y turística: el caso de dos localidades contrastantes en la provincia de Buenos Aires (Argentina)
    (2021) Pinassi, Andrés; Comparato, Gabriel
    El objetivo de esta investigación es analizar de manera comparada los procesos de construcción patrimonial y turística en las localidades bonaerenses de Tigre y Nicolás Levalle (Argentina), a la luz de los dilemas contemporáneos que se suscitan en el ámbito académico y de la gestión. En relación a la metodología, el trabajo adquiere un alcance explicativo y un enfoque mixto, con preponderancia cualitativa, caracterizándose por un razonamiento deductivo e inductivo que permite reflexionar de manera recíproca entre variables particulares y generales. Como resultado, las dos localidades indagadas fueron reconstruidas a partir de considerar: una acción histórica, relativa a los procesos de legitimación y selectividad del patrimonio y los atractivos turísticos; una acción dinámica, que puso en juego las transformaciones bajo nuevas formas de apropiación y uso del espacio; y una acción discursiva, que incorpora la dimensión simbólica y heterogénea en torno a la construcción patrimonial y turística, según la intervención de agentes específicos. A modo de conclusión, en esta investigación se enfatizó en los procesos de valorización turística del patrimonio, más allá de la descripción de los componentes histórico-culturales en sí mismos. En efecto, se buscó superar la mera casuística, para dar lugar a la articulación teórico-práctica en clave de contrastes. De allí que se visualizan diferentes discursos activados, que reflejan contextos históricos diversos, según la configuración socio-espacial de las localidades. Se observó que, dentro de un escenario de tensiones, objetivos e intereses distintos, elaccionar de ciertos actores sociales ha sido determinante para indagar los grados de consolidación y desarrollo turístico, al igual que los enfoques de gestión y los niveles de participación ciudadana.
  • Documento de conferencia
    Acceso Abierto
    Polimerosomas y sus potenciales aplicaciones
    (2020) Gangoiti, Maria Virginia; Besada, Lucas
    El Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM) se dedica al estudio de patologías óseas y metabólicas, así como a la aplicación de biomateriales tanto en ingeniería de tejidos para la reparación de lesiones osteoarticulares, como en sistemas del liberación de drogas. En este sentido, el desarrollo de los polimerosomas, que se llevó a cabo en conjunto con el grupo Macromoléculas del INIFTA, constituye un claro ejemplo del trabajo interdisciplinario que se realiza en el LIOMM. Los polimerosomas son vesículas formadas por copolímeros en bloque, que en el último tiempo han aumentado su importancia por la versatilidad en sus aplicaciones. Gracias a su capacidad para encapsular tanto compuestos hidrofóbicos como hidrofílicos, su gran estabilidad y la potencialidad para ser funcionalizados, estos sistemas representan el futuro en muchas ramas de la ciencia y la medicina. En este trabajo mostramos cómo a partir de la síntesis de un copolímero que posee un bloque hidrofílico central de polietilenglicol y dos bloques hidrofóbicos laterales de polibenzoato de vinilo, obtuvimos por autoensamblado vesículas poliméricas estables que poseen la capacidad de encapsular en su membrana componentes hidrofóbicos. Además destacamos la gran variedad de potenciales aplicaciones de dichos sistemas.
  • Artículo
    Acceso Abierto
    Insulin-like growth factor binding proteins from adult-hamster pancreatic islets: influence of glucose concentration
    (1997) Massa, L.; Cortizo, Ana María; Gagliardino, Juan José
    This study investigated the effect of glucose on insulin-like growth factor binding proteins (IGFBPs) in islets isolated from pancreas of adult hamsters and compared the response pattern with that of their serum IGFBPs. Serum samples and islets were obtained from adult normal male hamsters, and IGF-binding capacity was measured in aliquots of serum, sonicated islets, or conditioned medium using either 125I-hIGF-I or -II. IGFBPs were characterized in these samples by the ligand-blotting technique, and insulin was measured in conditioned medium by radioimmunoassay. Three IGFBP fractions were identified in serum, with relative molecular weights of 38, 30-33, and 24 kDa, while only two fractions of 30-33 and 24 kDa were identified in islets or in their conditioned medium. Islets cultured with 2 or 16 mM glucose for 48 h released more insulin in the presence of the higher glucose concentration. The binding capacity measured in the islet suspension or conditioned medium increased as a function of glucose concentration in the incubation medium. The IGFBPs present both in islets and conditioned medium had a 3- to 4-fold higher apparent affinity for IGF-II than IGF-I. The higher glucose concentration increased the intensity of the two IGFBP bands identified in the islet suspension by 2- to 3-fold. Our data show that two low-molecular-weight IGFBPs were released from adult hamster pancreatic islets, with a different distribution pattern from that of hamster serum, and that the amount of IGFBPs released by islets depended on the glucose concentration in the culture medium. Though not conclusive, these data suggest that IGFBPs may play a regulatory role in B-cell turnover in adult islets as they do in foetal islets.
  • Artículo
    Embargado
    Multiple modulators of the glucose-induced net calcium uptake by isolated islets
    (1984) Borelli, María Inés; Cortizo, Ana María; Gagliardino, Elma Edith P. de; Garcia, María Elisa; Gagliardino, Juan José
    Glucose-induced insulin secretion and net calcium uptake were simultaneously studied in isolated islets obtained from normal, adrenalectomized, ovariectomized and radiothyroidectomized rats, as well as from the corresponding hormone deprived rats following the administration of specific substitutive therapy. Both parameters were also studied in islets from normal rats incubated in the presence of Trifluoperazine (TFP). In all these unrelated experimental conditions simultaneous changes were obtained, observed in the release of insulin and the net calcium uptake elicited by glucose. Otherwise, the modifications of these two parameters obtained in the hormone deprived states were brought back to normal when the animals received the specific substitutive hormonal treatment. On the other hand, TFP also induces simultaneous diminution in both glucose-induced insulin release and net calcium uptake by isolated islets. On account of our results, we could suggest that the mechanism involved in the control of the glucose-induced net calcium uptake is actively modulated by adrenal and ovarian steroids and thyroid hormones as well as by calmodulin. Therefore, changes induced either in the level or activity of these modulators will modify the rate of influx and efflux of Ca2+ across the plasma membrane, with the consequent alteration in the mechanism of stimulus: secretion coupling of insulin.
  • Documento de conferencia
    Acceso Abierto
    Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral: un enfoque multidisciplinario para el tratamiento de osteopatías de origen metabólico
    (2017) Cortizo, Ana María; McCarthy, Antonio Desmond; Molinuevo, María Silvina; Gangoiti, Maria Virginia; Fernández, Juan Manuel
    El Laboratorio de Investigaciones en Osteopatías y Metabolismo Mineral (LIOMM) se creó en el año 2012 como una unidad multidisciplinaria dedicada a la investigación científico-tecnológica, con el fin de incrementar los conocimientos científicos, la educación y la extensión en el campo de las patologías óseas y metabólicas, así como su aplicación en la ingeniería de tejidos. Nuestras áreas de interés son: osteopatías, metabolismo mineral, diabetes mellitus, síndrome metabólico, ingeniería de tejido. Se abordan aspectos de la fisiopatología del esqueleto asociados con enfermedades metabólicas de alta prevalencia como la diabetes mellitus, síndrome metabólico y obesidad. Se investigan las posibles causas de estas osteopatías metabólicas, sus tratamientos con diferentes fármacos, así como terapia celular utilizando células progenitoras de médula ósea. Para contribuir al espectro terapéutico disponible para las distintas patologías oseocartilaginosas, se desarrollan y estudian matrices poliméricas que sirvan como sistemas de liberación controlada de drogas o como scaffolds para la reparación de tejido oseoarticular. Contamos con la colaboración de investigadores clínicos (osteólogos, endocrinólogos) del país, investigadores básicos (INIFTA, IFLYSIB, Universidad de Rosario) y grupos del extranjero, en particular de España (Universidad Politécnica de Valencia, Universidad de Oviedo, Instituto de Bioingeniería de Cataluña, IBEC) y de Estados Unidos (Universidad de Florida, Gainesville).
  • Artículo
    Acceso Abierto
    Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells
    (Hindawi Publishing Corporation, 2016) Chuguransky, Sara Rocío; Cortizo, Ana María; McCarthy, Antonio Desmond
    Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulindeficient Diabetes) on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization) and chondrogenesis (glycosaminoglycan production) of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects.The adipogenesis of BMPC (PPAR��, intracellular triglycerides, and lipase) was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a) decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b) increased bone marrow adiposity; and (c) deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis). Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC.
  • Artículo
    Acceso Abierto
    Efectos in vivo del ranelato de estroncio sobre células progenitoras de médula ósea de ratas diabéticas
    (Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM), 2016) Lino, Agustina Berenice; Fernández, Juan Manuel; Molinuevo, María Silvina; Cortizo, Ana María; McCarthy, Antonio Desmond
    La diabetes mellitus (DM) crónica se asocia con reducción en el contenido mineral óseo (osteopenia y osteoporosis). El objetivo de este trabajo fue evaluar la acción del ranelato de estroncio (RaSr) administrado por vía oral a animales control y diabéticos, sobre el potencial osteogénico de células progenitoras de médula ósea (CPMO). Dieciséis ratas Wistar macho jóvenes se dividieron en dos grupos: controles (C) y diabéticas (D) con destrucción parcial de células b-pancreáticas mediante inyecciones intraperitoneales consecutivas de nicotinamida y estreptozotocina. Siete días después de la inyección, cada grupo se subdividió: sin tratamiento, o tratadas oralmente con RaSr (625 mg/kg/día) durante seis semanas, luego de lo cual los animales fueron sacrificados. Las CPMO se obtuvieron de ratas de los cuatro grupos, por lavados del canal diafisario medular (húmero o fémur o ambos) y cultivo hasta confluencia en DMEM-10% FBS. La proliferación celular se evaluó mediante el ensayo de MTT. Luego las CPMO se replaquearon e incubaron en un medio osteogénico durante 14 días (fosfatasa alcalina [FAL] y colágeno tipo 1) o 21 días (mi- * Correo electrónico: mccarthy@biol.unlp.edu.ar neralización). Las CPMO del grupo C+RaSr mostraron un aumento significativo versus control en la proliferación (133%) y en la diferenciación osteogénica (colágeno 143%, FAL 168%, mineralización 117%). La DM (grupo D) disminuyó significativamente la proliferación y diferenciación osteoblástica de las CPMO. El tratamiento con RaSr (grupo D+RaSr) previno completamente estos efectos antiosteogénicos de la DM. Así, en nuestro modelo experimental in vivo, la DM disminuye el potencial osteogénico de CPMO, efecto que puede ser prevenido por un tratamiento oral con RaSr.
  • Artículo
    Acceso Abierto
    Guías Argentinas para el diagnóstico, la prevención y el tratamiento de la osteoporosis 2015
    (Fundación Revista Medicina, 2017) Schurman, León; Galich, Ana M.; González, Claudio; González, Diana; Messina, Osvaldo D.; Sedlinsky, Claudia; Uña, Claudia R.; Sánchez, Ariel
    La osteoporosis es una enfermedad en constante crecimiento y que afecta a más de 200 millones de personas en todo el mundo. Nuestras recomendaciones son guías para el diagnóstico, la prevención y tratamiento, pero no normas para las decisiones clínicas en casos individuales. El médico debe adaptarlas a situaciones en la práctica clínica cotidiana, incorporando factores personales que trascienden los límites de estas guías y hacen al saber y al arte de la práctica médica. Como todo conocimiento científico, deben ser actualizadas periódicamente a medida que se adquieran nuevas, mejores y más efectivas herramientas diagnósticas y terapéuticas.
  • Artículo
    Acceso Abierto
    Effect of metformin on bone marrow progenitor cell differentiation: in vivo and in vitro studies
    (2010) Molinuevo, M. Silvina; Schurman, Leon; McCarthy, Antonio Desmond; Cortizo, Ana María; Tolosa, María J.; Gangoiti, M. Virginia; Arnol, Veronica; Sedlinsky, Claudia
    Diabetes mellitus is associated with bone loss. Patients with type 2 diabetes are frequently treated with oral antidiabetic drugs such as sulfonylureas, biguanides, and thiazolidinediones. Rosiglitazone treatment has been shown to increase adipogenesis in bone marrow and to induce bone loss. In this study we evaluated the effect of in vivo and in vitro treatment with metformin on bone marrow progenitor cells (BMPCs), as well as the involvement of AMPK pathway in its effects. The in vitro effect of coincubation with metformin and rosiglitazone on the adipogenic differentiation of BMPCs also was studied. In addition, we evaluated the effect of in vivo metformin treatment on bone regeneration in a model of parietal lesions in nondiabetic and streptozotocin-induced diabetic rats. We found that metformin administration both in vivo and in vitro caused an increase in alkaline phosphatase activity, type I collagen synthesis, osteocalcin expression, and extracellular calcium deposition of BMPCs. Moreover, metformin significantly activated AMPK in undifferentiated BMPCs. In vivo, metformin administration enhanced the expression of osteoblast-specific transcription factor Runx2/Cbfa1 and activation of AMPK in a time-dependent manner. Metformin treatment also stimulated bone lesion regeneration in control and diabetic rats. In vitro, metformin partially inhibited the adipogenic actions of rosiglitazone on BMPCs. In conclusion, our results indicate that metformin causes an osteogenic effect both in vivo and in vitro, possibly mediated by Runx2/Cbfa1 and AMPK activation, suggesting a possible action of metformin in a shift toward the osteoblastic differentiation of BMPCs.
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    Alendronate induces anti-migratory effects and inhibition of neutral phosphatases in UMR106 osteosarcoma cells
    (2007) Molinuevo, M.S.; Bruzzone, L.; Cortizo, Ana María
    Bisphosphonates are nonhydrolysable pyrophosphate analogues that prevent bone loss in several types of cancer. However, the mechanisms of anticancer action of bisphosphonates are not completely known. We have previously shown that nitrogen-containing bisphosphonates directly inhibit alkaline phosphatase of UMR106 rat osteosarcoma cells. In this study, we evaluated the effects of alendronate on the migration of UMR106 osteosarcoma using a model of multicellular cell spheroids, as well as the alendronate effect on neutral phosphatases. Alendronate significantly inhibited the migration of osteoblasts in a dose-dependent manner (10(-6)-10(-4) M). This effect was also dependent on calcium availability. The spheroid morphology and distribution of actin fibers were also affected by alendronate treatment. Alendronate dose-dependently inhibited neutral phosphatase activity in cell-free osteoblastic extracts as well as in osteoblasts in culture. Our results show that alendronate inhibits cell migration through mechanisms dependent on calcium, and that seem to involve inhibition of phosphotyrosine-neutral-phosphatases and disassembly of actin stress fibers.