Alkaline phosphatase

About: Alkaline phosphatase is a research topic. Over the lifetime, 20218 publications have been published within this topic receiving 540547 citations. The topic is also known as: Alkaline_phosphatase & IPR001952.

BMP responsiveness in human mesenchymal stem cells.

Abstract: Bone morphogenetic proteins (BMPs) are well known to induce bone formation in animal models and can promote osteogenesis in cultures of multipotential mesenchymal stem cells (MSC) isolated from rat and mouse bone marrow. However, clinical trials of BMPs suggest that BMPs are relatively ineffective inducers of osteogenesis in humans. Recent studies from our lab indicate that when human bone marrow MSC are placed in primary culture, osteogenesis can be induced by dexamethasone (Dex), but not by BMP-2, -4, or -7. We have therefore investigated components of BMP signaling pathways in human MSC. First passage cells, derived from the bone marrow of patients undergoing hip replacement surgery, were cultured with ascorbate phosphate and treated with 100 nM dexamethasone (Dex), 100 ng/ml BMP, or both. After 6 days, alkaline phosphatase activity of cell extracts was measured, and RNA was extracted for RT-PCR analysis of mRNA levels. Among human MSC samples from more than a dozen patients, only one patient sample showed significantly elevated alkaline phosphatase after exposure to BMP; the rest responded to Dex but not BMP. Analysis of mRNA from cultured human MSC indicated that, while Dex treatment caused increased levels of mRNA for alkaline phosphatase, BMP did not. Noggin is a BMP-binding protein that is upregulated by BMPs. BMP-treated human MSC cultures that did not show increased alkaline phosphatase did express elevated levels of noggin mRNA, indicating that the cells are capable of some BMP response. Our results suggest that BMP signaling in mesenchymal stem cells utilizes more than one system for transcriptional activation. The inability of most human MSC to activate transcription of the alkaline phosphatase gene implies that a defect exists in the system required for induction of the osteoblast phenotype.

Molecular mechanisms of accommodation in Escherichia coli to toxic levels of Cd2

Abstract: Cells of Escherichia coli strain B develop large intracellular vacuoles and exhibit an abnormally long lag phase when inoculated into a defined medium to glucose and salts containing 3 times 10-6 M Cd2+. Early in this lag, about 95% of the cells fail to form colonies when plated on nutrient broth-NaCl-agar. Prior to the initiation of proliferation, the morphology of these cells becomes normal. They regain viability in the absence of deoxyribonucleic acid replication. The rate and extent of growth are normal once proliferation begins. This reversible phenomenon of accommodation to a growth-inhibiting concentration of Cd2+ does not appear to result from a selection of mutant cells. Cells which are proliferating in the presence of Cd2+ accumulate the ion to a very high concentration. In membranes and 31% in the cytoplasm. In unaccommodated cells, the figures are 2%, 75%, and 23%, respectively. The activity of alkaline phosphatase, a zinc-metalloenzyme which is inhibited by cadmum and is located between cell wall and membrane, is not abnormally low in accommodated cells, suggesting that the cadmim is compartmentalized in these cells. Molecular sieve chromatography of cell extracts shows that the Cd2+ is associated with two classes of macromolecules. It appears that accommodation of E. coli to the presence of Cd2+ involves exclusion of the ion from the cell and reversal of damage caused by prior exposure to the ion.