In vitro effects and mechanisms of Humulus lupulus extract on bone marrow progenitor cells and endothelial cells.

Osteoporosis is the most common metabolic bone disorder and is associated with a high incidence of fractures. Angiogenesis and adequate blood flow are important during bone repair and maintenance. Estrogens play a key role in bone formation, in the prevention of bone resorption and vasculature maintenance. Hormone replacement therapy (HRT) has been used with great benefits for bone fracture prevention but has been linked to the development of serious important side effects, including cancer and stroke. Phytoestrogens are an attractive alternative to HRT because their chemical structure is similar to estradiol but, they could behave as selective modulators: acting as antagonists of estrogen receptors in the breast and endometrium and as agonists in the vascular endothelium and bone. Hops contain a wide variety of phytoestrogens that have individually been shown to possess estrogenic activity by either blocking or mimicking. In this study we have to evaluate the in vitro effects and mechanisms of action of hops extracts on the osteogenic and adipogenic capacity of bone marrow progenitor cells (BMPCs), and the angiogenic potential of EA.hy926 endothelial cells. We show that hops extracts increase the proliferative capacity of BMPCs and promote their osteogenic differentiation while decreasing their pro-osteoclastogenic capacity; and that these effects are mediated by the MAPK pathway. Additionally, hops extracts prevent the adipogenic differentiation of BMPCs and promote endothelial cell activity, by mechanisms also partially mediated by MAPK.

Osteoporosis and Alzheimer´s disease (or Alzheimer´s disease and Osteoporosis).

Alzheimer's disease (AD) and osteoporosis are two diseases that mainly affect elderly people, with increases in the occurrence of cases due to a longer life expectancy. Several epidemiological studies have shown a reciprocal association between both diseases, finding an increase in incidence of osteoporosis in patients with AD, and a higher burden of AD in osteoporotic patients. This epidemiological relationship has motivated the search for molecules, genes, signaling pathways and mechanisms that are related to both pathologies. The mechanisms found in these studies can serve to improve treatments and establish better patient care protocols.

Skeletal Effects of a Prolonged Oral Metformin Treatment in Adult Wistar Rats.

INTRODUCTION: We previously showed that a 3-week oral metformin (MET) treatment enhances the osteogenic potential of bone marrow stromal cells (BMSCs) and improves several bone histomorphometric parameters in Wistar rats with metabolic syndrome (MetS). However, the skeletal effects of extended periods of MET need to be completely elucidated. Hence, in this study, the impact of a prolonged (3-month) MET treatment was investigated on bone architecture, histomorphometric and biomechanics variables, and osteogenic potential of BMSCs in Wistar rats with or without MetS. MATERIALS AND METHODS: Young male Wistar rats (n=36) were randomized into four groups (n=9) that received either 20% fructose (F), MET (MET), F plus MET treatments (FMET), or drinking water alone (Veh). Rats were euthanized, blood was collected, and bones were dissected and processed for peripheral quantitative computed tomography (pQCT) analysis, static and dynamic histomorphometry, and bone biomechanics. In addition, BMSCs were isolated to determine their osteogenic potential. RESULTS: MET affected trabecular and cortical bone, altering bone architecture and biomechanics. Furthermore, MET increased the pro-resorptive profile of BMSCs. In addition, fructose-induced MetS practically did not affect the the structural or mechanical variables of the skeleton. CONCLUSION: A 3-month treatment with MET (with or without MetS) affects bone architecture and biomechanical variables in Wistar rats.

Síndrome metabólico, metformina y hueso / Metabolic syndrome, metformin and bone

El síndrome metabólico se define como un trastorno heterogéneo y multifactorial con riesgo cardiovascular elevado. Actualmente se encuentra en franco crecimiento debido al sedentarismo y la ingesta rica en grasas y azúcares. Su tratamiento incluye la indicación de cambios en el estilo de vida, con realización de actividad física y una alimentación saludable e hipocalórica. Cuando esto no es eficaz, se pueden utilizar diferentes fármacos, y entre los más prescriptos se encuentra la metformina, caracterizada por su acción insulino-sensibilizante. Numerosos trabajos han estudiado la vinculación del síndrome metabólico con el tejido óseo. Se demostró como resultado general, aunque no concluyente, que dicho síndrome se asocia con una disminución de la densidad mineral ósea y un aumento en la incidencia de fracturas osteoporóticas. Una de las limitaciones de estos estudios clínicos estaría ligada a la gran heterogeneidad de los pacientes con síndrome metabólico. Por otra parte, y dado que diversos estudios preclínicos han sugerido posibles acciones osteogénicas de la metformina, se ha investigado el posible efecto óseo de un tratamiento con este fármaco en personas con hiperglucemia o disglucemia. Varios estudios clínicos muestran que este efecto sería nulo o, en algunos casos, de carácter protector para el sistema óseo. No obstante, se debería tener precaución en el uso de dicho fármaco en pacientes que necesiten dosis altas y/o posean riesgo elevado de fractura, ya que sus altas concentraciones podrían tener consecuencias negativas sobre el metabolismo óseo. (AU)

Metabolic syndrome is defined as a heterogeneous and multifactorial disorder with high cardiovascular risk. Its incidence is currently growing due to sedentary lifestyles and diets with a high intake of fats and sugars. Treatment for metabolic syndrome begins with changes in lifestyle, such as physical activity and a healthy and hypocaloric diet. When this is not effective, different drugs can be used, and one of the most frequently prescribed is the insulin-sensitizer metformin. Numerous investigations have evaluated the possible link between metabolic syndrome and alterations in bone metabolism. Although not conclusive, most clinical studies point to an association between metabolic syndrome, a decrease in bone mineral density and an increase in the incidence of osteoporotic fractures. However, an important limitation of these studies is the great heterogeneity of individuals with metabolic syndrome. In view of preclinical research indicating possible osteogenic actions of metformin, the effects on bone of metformin has been evaluated in patients with hyperglycemia. Most studies have found either no effect on fracture incidence, or a mild protective action. However, since elevated concentrations of metformin might negatively affect bone metabolism, caution should be taken when prescribing this drug for patients who require high doses, and/or have an excess fracture risk. (AU)