Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI).

Background: Lysinuric protein intolerance (LPI [MIM 222700]) is an aminoaciduria with defective transport of cationic amino acids in epithelial cells in the small intestine and proximal kidney tubules due to mutations in the SLC7A7 gene. LPI is characterized by protein malnutrition, failure to thrive and hyperammonemia. Many patients also suffer from combined hyperlipidemia and chronic kidney disease (CKD) with an unknown etiology.

Nonuniform temperature rise in in vitro osteoblast ultrasound exposures with associated bioeffect.

There is a growing interest to use ultrasound to stimulate cellular material in vitro conditions for the treatment of musculoskeletal disorders. However, the beneficial effect resulting from ultrasound exposure is not accurately specified. Many in vitro ultrasound setups are very vulnerable to temperature elevation due to sound absorption, sound reflections, and inadequate heat transfer.

Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells.

The benefit from an ultrasound (US) exposure for fracture healing has been clearly shown. However, the molecular mechanisms behind this effect are not fully known. Recently, the canonical Wnt signaling pathway has been recognized as one of the essential regulators of osteoblastogenesis and bone mass, and thereby considered crucial for bone health.

Dioxins interfere with differentiation of osteoblasts and osteoclasts.

We have previously shown that the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone growth, modelling and mechanical strength in vivo. In this study, we utilized differentiation of bone marrow stem cells to osteoblasts and osteoclasts as a model system to study the effects of TCDD on bones. Stem cells were isolated from bone marrow of femurs and tibias of rats and mice.

Calreticulin mediated glucocorticoid receptor export is involved in beta-catenin translocation and Wnt signalling inhibition in human osteoblastic cells.

Wnt signalling pathway is a multicomponent cascade involving interaction of several proteins and found to be important for development and function of various cells and tissues. There is increasing evidence that the Wnt/beta-catenin pathway constitutes also one of the essential molecular mechanisms controlling the metabolic aspects of osteoblastic cells. However, in bone, glucocorticoids (GCs) have been reported to weaken Wnt signalling.

Genome-wide microarray analysis of MG-63 osteoblastic cells exposed to ultrasound.

It is well documented that low intensity pulsed ultrasound can be clinically used to accelerate bone fracture healing. Additionally, in vitro studies have shown that ultrasound can, for instance, increase mineralization, collagen production and alkaline phosphatase activity in osteoblasts. Despite the extensive research on the subject, the exact mechanism of ultrasound effect on bone cell gene regulation has not yet been deduced.

Wnt and steroid pathways control glutamate signalling by regulating glutamine synthetase activity in osteoblastic cells.

Glutamate signalling has recently been found functional also outside the central nervous system, especially in bone. Glutamate is converted to glutamine by glutamine synthetase (GS), which is therefore able to regulate intracellular concentrations of glutamate. We previously characterized the induction of GS expression by glucocorticoids (GCs) in human osteoblast-like cells.

Estrogen receptor alpha genotype confers interindividual variability of response to estrogen and testosterone in mesenchymal-stem-cell-derived osteoblasts.

Hormone replacement therapy is effectively used to prevent postmenopausal bone loss. Variation in response to the therapy is, however, frequently seen. In addition, the direct effects of sex steroids on isolated human bone marrow stromal cells have been reported to vary depending on the donor, but the biological mechanisms are not understood.