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)

Skeletal stem and progenitor populations provide a platform for cell-based tissue regeneration strategies. Optimized conditions for ex vivo expansion will be critical and use of serum-free culture may allow enhanced modelling of differentiation potential. Maintenance of human foetal femur-derived cells in a chemically defined medium (CDM) with activin A and fibroblast growth factor-2 generated a unique undifferentiated cell population in comparison to basal cultures, with significantly reduced amino acid depletion, appearance and turnover, reduced alkaline phosphatase (ALP) activity and loss of type I and II collagen expression demonstrated by fluorescence immunocytochemistry. Microarray analysis demonstrated up-regulation of CLU, OSR2, POSTN and RABGAP1 and down-regulation of differentiation-associated genes CRYAB, CSRP1, EPAS1, GREM1, MT1X and SRGN as validated by quantitative real-time polymerase chain reaction. Application of osteogenic conditions to CDM cultures demonstrated partial rescue of ALP activity. In contrast, the addition of bone morphogenetic protein-2 (BMP-2) resulted in reduced ALP levels, increased amino acid metabolism and, strikingly, a marked shift to a cobblestone-like cellular morphology, with expression of SOX-2 and SOX-9 but not STRO-1 as shown by immunocytochemistry, and significantly altered expression of metabolic genes (GFPT2, SC4MOL and SQLE), genes involved in morphogenesis (SOX15 and WIF1) and differentiation potential (C1orf19, CHSY-2,DUSP6, HMGCS1 and PPL). These studies demonstrate the use of an intermediary foetal cellular model for differentiation studies in chemically defined conditions and indicate the in vitro reconstruction of the mesenchymal condensation phenotype in the presence of BMP-2, with implications therein for rescue studies, screening assays and skeletal regeneration research.
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PMID:Derivation of a novel undifferentiated human foetal phenotype in serum-free cultures with BMP-2. 1943 13

Dental follicle cells (DFCs) differentiate into cementoblasts or osteoblasts under appropriate triggering. However, the mechanism(s) for osteogenic differentiation of DFCs are still unclear. The purpose of this study was to examine the effects of dental papilla-derived human dental pulp cells (hDPCs) on osteogenic differentiation of human DFCs (hDFCs) in vitro and in vivo and to compare gene expression in hDFCs in the presence or absence of hDPCs. To evaluate the osteogenic differentiation of hDFCs induced by hDPCs, hDFCs were cultured in osteogenic medium with or without hDPCs-conditioned medium (CM) in vitro and the cells transplanted into the subcutaneous tissue of immunodeficient mice in vivo. The hDPCs-CM enhanced alkaline phosphatase promoter activity of hDFCs in osteogenic culture. The expression of several osteoblast marker genes was increased in hDFCs treated with hDPCs-CM compared to hDFCs in normal medium. The hDFCs induced by hDPCs-CM also produced more calcified nodules than hDFCs in normal medium. In transplantation experiments, hDPCs-CM promoted the osteogenic induction and bone formation of hDFCs. Microarray analysis and quantitative real-time PCR showed that osteogenesis-related genes including WNT2, VCAN, OSR2, FOSB, and POSTN in hDFCs were significantly upregulated after induction by hDPCs-CM compared to hDFCs in normal medium. These findings indicate that hDPCs could increase the expression of osteogenic genes in hDFCs and stimulate their osteogenesis and could be a cellular resource for bone regeneration therapy when induced by hDPCs-derived factors.
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PMID:Osteogenic differentiation and gene expression profile of human dental follicle cells induced by human dental pulp cells. 2552 56