Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts

Insulin receptor substrates (IRS-1 and IRS-2) are essential for intracellular signaling by insulin and insulin-like growth factor-I (IGF-I), anabolic regulators of bone metabolism. Although mice lacking the IRS-2 gene (IRS-2−/− mice) developed normally, they exhibited osteopenia with decreased bone formation and increased bone resorption. Cultured IRS-2−/− osteoblasts showed reduced differentiation and matrix synthesis compared with wild-type osteoblasts. However, they showed increased receptor activator of nuclear factor κB ligand (RANKL) expression and osteoclastogenesis in the coculture with bone marrow cells, which were restored by reintroduction of IRS-2 using an adenovirus vector. Although IRS-2 was expressed and phosphorylated by insulin and IGF-I in both osteoblasts and osteoclastic cells, cultures in the absence of osteoblasts revealed that intrinsic IRS-2 signaling in osteoclastic cells was not important for their differentiation, function, or survival. It is concluded that IRS-2 deficiency in osteoblasts causes osteopenia through impaired anabolic function and enhanced supporting ability of osteoclastogenesis. We propose that IRS-2 is needed to maintain the predominance of bone formation over bone resorption, whereas IRS-1 maintains bone turnover, as we previously reported; the integration of these two signalings causes a potent bone anabolic action by insulin and IGF-I

Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: A comparison with teriparatide

Abaloparatide (ABL) is a novel 34-amino acid peptide analog of parathyroid hormone-related protein. In clinical studies, although ABL showed a greater bone mineral density (BMD) increase than teriparatide (TPTD, human parathyroid hormone 1-34), the responses of ABL to bone formation and resorption markers were weaker, making it difficult to understand the relationship between the bone anabolic window (increase in bone formation versus resorption) and bone mass. In the present study, the effects of ABL and TPTD were compared in mice. Given that the rate of bone turnover is higher in rodents than in humans, the comparison was made with several administration regimens providing equivalent daily dosages: once daily (QD, 30 mu g/kg every 24 h), twice daily (BID, 15 mu g/kg every 12 h), or three times a day (TID, 10 mu g/kg every 8 h). Frequent administration of ABL showed higher BMD with enhancement of trabecular and cortical bone mass and structures than that of TPTD, consistent with the clinical results seen with once daily administration. ABL increased bone formation marker levels more than TPTD with more frequent regimens, while bone resorption marker levels were not different between ABL and TPTD in all regimens. Analysis of bone histomorphometry and gene expression also suggested that ABL increased bone formation more than TPTD, while the effect on bone resorption was almost comparable between ABL and TPTD. The bone anabolic windows calculated from bone turnover markers indicated that ABL enhanced the anabolic windows more than TPTD, leading to a robust increase in BMD. The mechanism by which ABL showed a better balance of bone turnover was suggested to be partly due to the enhanced remodeling-based bone formation involved in Ephb4. Taken together, our findings would help elucidate the mechanism by which ABL shows excellent BMD gain and reduction of fractures in patients with osteoporosis

Tài liệu luyện thi năng lực tiếng Nhật N3 = Kanji N3

163 tr. : minh họa; 27 cm

Uso de inhibidores de tak1 en la prevención y tratamiento del fracaso de la membrana peritoneal

[EN] The invention relates to the use of TAKl inhibitors for the preparation of a drug for the prevention and treatment of peritoneal membrane failure, said use preventing and reversing the mesenchymal-epithelial transition experienced by the mesothelial cells of the peritoneum during peritoneal dialysis treatment. In addition, the invention relates to the use of a TAKl expression product or of its activity as a biomarker for determining peritoneal fibrosis. The invention further relates to the method for obtaining data that can be used in the diagnosis and/or prognosis of peritoneal fibrosis and to a method for predicting the progression ofperitoneal fibrosis. The invention also relates to the use of a kit comprising the sequence that codes for TAKl or the protein for the diagnosis of peritoneal fibrosis.[ES] La presente invención se refiere al uso de inhibidores de TAKl para la preparación de un medicamento para la prevención y tratamiento del fracaso de la membrana peritoneal. Donde dicho uso previene y revierte la transición epitelio mesénquima que sufren las células mesoteliales del peritoneo durante el tratamiento de diálisis peritoneal. También, al uso de un producto de expresión de TAKl o de su actividad como biomarcador para la detenninación de fibrosis peritoneal. Al método de obtención de datos útiles en el diagnóstico y/o pronóstico de la fibrosis peritoneal; un método para predecir la progresión de la fibrosis peritoneal. Así como el uso de un kit que comprende la secuencia que codifica para TAKl o la proteína para el diagnóstico de la fibrosis peritoneal.Peer reviewedCentro Nacional de Investigaciones Cardiovasculares, Consejo Superior de Investigaciones Científicas, Centro de Investigación Biomédica en Red:Enfermedades Hepáticas y DigestivasA2 Solicitud de patente sin informe sobre el estado de la técnic

Additional file 6: Table S5. of Genome analysis of the foxtail millet pathogen Sclerospora graminicola reveals the complex effector repertoire of graminicolous downy mildews

TPM values of DEGs encoding putative secreted proteins and cluster numbers from clustering analyses. (XLSX 68 kb

Additional file 16: of Genome analysis of the foxtail millet pathogen Sclerospora graminicola reveals the complex effector repertoire of graminicolous downy mildews

RXLR-like genes predicted in genome of Sclerospora graminicola and their expression levels during infection. (XLSX 82 kb