Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Explant cultures of adult human trabecular bone fragments give rise to osteoblastic cells, that are known to express osteoblast-related genes and mineralize extracellular matrix. These osteoblastic cells have also been shown to undergo adipogenesis in vitro and chondrogenesis in vivo. Here we report the in vitro developmental potential of adult human osteoblastic cells (hOB) derived from explant cultures of collagenase-pretreated trabecular bone fragments. In addition to osteogenic and adipogenic differentiation, these cells are capable of chondrogenic differentiation in vitro in a manner similar to adult human bone marrow-derived mesenchymal progenitor cells. High-density pellet cultures of hOB maintained in chemically defined serum-free medium, supplemented with transforming growth factor-beta1, were composed of morphologically distinct, chondrocyte-like cells expressing mRNA transcripts of collagen types II, IX and X, and aggrecan. The cells within the high-density pellet cultures were surrounded by a sulfated proteoglycan-rich extracellular matrix that immunostained for collagen type II and proteoglycan link protein. Osteogenic differentiation of hOB was verified by an increased number of alkaline phosphatase-positive cells, that expressed osteoblast-related transcripts such as alkaline phosphatase, collagen type I, osteopontin and osteocalcin, and formed mineralized matrix in monolayer cultures treated with ascorbate, beta-glycerophosphate, and bone morphogenetic protein-2. Adipogenic differentiation of hOB was determined by the appearance of intracellular lipid droplets, and expression of adipocyte-specific genes, such as lipoprotein lipase and peroxisome proliferator-activated receptor gamma2, in monolayer cultures treated with dexamethasone, indomethacin, insulin and 3-isobutyl-1-methylxanthine. Taken together, these results show that cells derived from collagenase-treated adult human trabecular bone fragments have the potential to differentiate into multiple mesenchymal lineages in vitro, indicating their developmental plasticity and suggesting their mesenchymal progenitor nature.
 ...
PMID:Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. 1238 74

Notch receptors are single pass transmembrane receptors activated by membrane-bound ligands with a role in cell proliferation and differentiation. As Notch 1 and 2 mRNAs are expressed by osteoblasts and induced by cortisol, we postulated that Notch could regulate osteoblastogenesis. We investigated the effects of retroviral vectors directing the constitutive expression of the Notch 1 intracellular domain (NotchIC) in murine ST-2 stromal and in MC3T3 cells. NotchIC overexpression was documented by increased Notch 1 transcripts and activity of the Notch-dependent Hairy Enhancer of Split promoter. In the presence of bone morphogenetic protein-2 (BMP-2), ST-2 cells differentiated toward osteoblasts forming mineralized nodules, and Notch 1 opposed this effect and decreased the expression of osteocalcin, type I collagen, and alkaline phosphatase transcripts and Delta2Delta FosB protein. Further, NotchIC decreased Wnt/beta-catenin signaling. As cells differentiated in the presence of BMP-2, they underwent apoptosis, and Notch opposed this event. In the presence of cortisol, NotchIC induced the formation of mature adipocytes and enhanced the effect of cortisol on adipsin, peroxisome proliferator-activated receptor-gamma2 and CCAAT enhancer binding protein alpha and delta mRNA levels. NotchIC also opposed MC3T3 cell differentiation and the expression of a mature osteoblastic phenotype. In conclusion, NotchIC impairs osteoblast differentiation and enhances adipogenesis in stromal cell cultures.
 ...
PMID:Notch 1 impairs osteoblastic cell differentiation. 1296 86

Interconversion of bone marrow osteoblasts and adipocytes has been reported previously. However, the osteogenic potential of extramedullary adipocytes is not known. Thus, we incubated a pure culture of human subcutaneous adipocytes in control medium for 1-2 weeks. Afterward, the cells were incubated in either osteoblast medium (OB medium) containing various combinations of calcitriol, dexamethasone, ascorbic acid, and beta-glycerophosphate or in adipocyte medium (AD medium) containing HEPES, biotin, pantothenate, insulin, triiodothyronine, dexamethasone, and isobutylmethylxanthine for 4 weeks. Expression of osteoblastic and adipocytic phenotypes was examined by determination of lineage-specific mRNA markers and in vitro adipocyte and osteoblast formation. Cells were also implanted, mixed with hydroxyapatite-tricalcium phosphate powder, in the subcutaneous tissue of immunodeficient mice in order to assess in vivo bone formation potential. One week after incubation in control medium, cells formed fusiform elongated fibroblast-like cells. In OB medium, cells stained positive for alkaline phosphatase (AP) and expressed mRNAs encoding Cbfa1/Runx2, AP, and osteocalcin. In AD medium cells reacquired adipocyte morphology with multilocular lipid-filled cells. Also, the cells expressed adipocyte-specific mRNA markers: lipoprotein lipase and peroxisome proliferator-activated receptor gamma2. Bone was formed only in the in vivo implants of cells incubated in OB medium. In conclusion, extramedullary adipocytes can transdifferentiate to bone-forming cells. Because of their ease of isolation, adipocytes may be good candidates for tissue-engineering protocols aimed at creating bone tissue for the repair of nonunion fractures and large bone defects.
 ...
PMID:Subcutaneous adipocytes can differentiate into bone-forming cells in vitro and in vivo. 1516 55

Decreased bone mass, osteoporosis, and increased fracture rates are common skeletal complications in patients with insulin-dependent diabetes mellitus (IDDM; type I diabetes). IDDM develops from little or no insulin production and is marked by elevated blood glucose levels and weight loss. In this study we use a streptozotocin-induced diabetic mouse model to examine the effect of type I diabetes on bone. Histology and microcomputed tomography demonstrate that adult diabetic mice, exhibiting increased plasma glucose and osmolality, have decreased trabecular bone mineral content compared with controls. Bone resorption could not completely account for this effect, because resorption markers (tartrate-resistant acid phosphatase 5b, urinary deoxypyridinoline excretion, and tartrate-resistant acid phosphatase 5 mRNA) are unchanged or reduced at 2 and/or 4 wk after diabetes induction. However, osteocalcin mRNA (a marker of late-stage osteoblast differentiation) and dynamic parameters of bone formation were decreased in diabetic tibias, whereas osteoblast number and runx2 and alkaline phosphatase mRNA levels did not differ. These findings suggest that the final stages of osteoblast maturation and function are suppressed. We also propose a second mechanism contributing to diabetic bone loss: increased marrow adiposity. This is supported by increased expression of adipocyte markers [peroxisome proliferator-activated receptor gamma2, resistin, and adipocyte fatty acid binding protein (alphaP2)] and the appearance of lipid-dense adipocytes in diabetic tibias. In contrast to bone marrow, adipose stores at other sites are depleted in diabetic mice, as indicated by decreased body, liver, and peripheral adipose tissue weights. These findings suggest that IDDM contributes to bone loss through changes in marrow composition resulting in decreased mature osteoblasts and increased adipose accumulation.
 ...
PMID:Increased bone adiposity and peroxisomal proliferator-activated receptor-gamma2 expression in type I diabetic mice. 1590 21

We investigated the effect of tigogenin on adipocytic and osteoblastic differentiation in mouse bone marrow stromal cells (BMSCs). Tigogenin enhanced the proliferation of BMSCs significantly. Tigogenin treatment reduced the adipogenic induction of lipid accumulation, visfatin secretion, and the expressions of peroxisome proliferation-activated receptor (PPAR)gamma2 and adipocyte fatty acid-binding protein (ap)2. Moreover, tigogenin had no effect on the mitotic clonal expansion. On the other hand, tigogenin significantly elevated alkaline phosphatase (ALP) activity and the expressions of Cbfa1, collagen type I (COL I) and osteocalcin (OCN), as well as the content of matrix calcium in BMSCs. Further, SB-203580 antagonized the tigogenin-promoted osteogenesis. These observations suggested that tigogenin may modulate differentiation of BMSCs to cause a lineage shift away from the adipocytes and toward the osteoblasts, which is at least mediated by inhibition of PPARgamma and via p38 MAPK pathway, and is a potential drug preventing the development of osteoporosis and the related disorders.
 ...
PMID:Tigogenin inhibits adipocytic differentiation and induces osteoblastic differentiation in mouse bone marrow stromal cells. 1736 41

Mesenchymal stem cells are pluripotent progenitors that could be found in human bone marrow. Mesenchymal stem cells are capable of renewing themselves without differentiation in long-term culture. These cells also have low immunogenicity and can suppress alloreactive T cell responses. In the current study, mesenchymal stem cells isolated and propagated previously from the bone marrow of a megaloblastic anaemia patient were tested for their capabilities to differentiate into adipocytes, chondrocytes and osteoblasts in vitro. The differentiated cells were determined by Oil Red O, Alcian Blue-PAS and Alizarin Red S staining, and reverse transcriptase-polymerase chain reaction to determine the expression of mRNA specific for adipogenesis, chondrogenesis and osteogenesis. The results showed that the fibroblast-like cells were capable of differentiating into adipocytes, chondrocytes and osteoblasts upon chemical induction. The adipocytes, chondrocytes and osteoblasts were stained positively to Oil Red O, Alcian Blue-PAS and Alizarin Red S respectively. The differentiated cells were also found to express mRNA specific for adipogenesis ('peroxisome proliferation-activated receptor gamma2' and lipoprotein lipase), chondrogenesis (collagen type II) and osteogenesis (osteocalcin, osteopontin and alkaline phosphatase). In conclusion, this research has successfully isolated fibroblast-like cells from human bone marrow and these cells demonstrated morphological, cytochemical and immunochemical characteristics similar to mesenchymal stem cells. These cells maintain their proliferative properties and could be differentiated into the mesoderm lineage. The success of this study is vital because mesenchymal stem cells can be used in cellular therapy to regenerate or replace damaged tissues, or as a vehicle for therapeutic gene delivery in the future.
 ...
PMID:In-vitro differentiation study on isolated human mesenchymal stem cells. 1910 6

The aim of this study was to determine if treatment with reversine, a purine analog, promoted generation of skeletal progenitor cells from lineage-committed annulus fibrosus cells. Reversine modulated cell growth, morphology, and the actin cytoskeleton of annulus fibrosus cells. Microarray profiling coupled with Ingenuity Pathway Analysis revealed that reversine treatment resulted in a significant expression change in many genes including those required for cell-cell interaction, cell movement, cell growth, and development. Further analysis revealed that there was involvement of gene networks concerned with cellular assembly and organization, DNA replication and repair, tissue morphology, and cell-to-cell signaling. The gene expression profile was dependent on reversine concentration. In osteogenic media, cells pretreated with 300 nM reversine exhibited an increased induction in alkaline phosphatase activity and enhanced expression of alkaline phosphatase, bone sialoprotein, osteocalcin, and collagen type I mRNA. Maintained in adipogenic media, the reversine-pretreated annulus cells displayed evidence of adipogenic differentiation: accumulation of cytosolic lipid droplets and increased expression of PPAR-gamma2, LPL, and Fabp mRNA. In chondrogenic media, cells pretreated with reversine exhibited marked increase in the induction of aggrecan, collagen types II, IX, and XI, and versican. It is concluded that reversine treatment induced annulus fibrosus cell plasticity and promoted their differentiation along mesenchymal lineages. This agent could be used to generate skeletal progenitor cells to orchestrate the repair of the intervertebral disc.
 ...
PMID:Reversine enhances generation of progenitor-like cells by dedifferentiation of annulus fibrosus cells. 1994 6


<< Previous 1 2