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

Osteopenia is a complicating problem that may occur during and after treatment for childhood malignancy. Clinical studies suggest that chemotherapeutic agents directly affect osteoblasts in vivo. Since combinations of agents are used for treatment, we individually investigated the chemosensitivity of human osteoblast-like cells to 11 of the chemotherapeutic agents used. The relative chemosensitivity of osteoblast-like cells representing different stages of cell differentiation was also examined. Cell numbers were evaluated following culture of an established human osteoblast-like cell line (MG63) for 3 days with clinically relevant concentrations of the chemotherapeutic agents. The chemosensitivity of MG63 cells was compared to that of a human osteoprogenitor cell line (HCC1) and primary osteoblast-like (HOB) cells derived from pediatric bone. Cell numbers were reduced by all agents in all cell types, although there was a varied response between agents at equimolar concentrations. In MG63 cells the lowest concentration of agent significantly reducing cell numbers varied between agents, for example, methotrexate (10(-7) M), vincristine (10(-9) M), and etoposide (10(-7) M) (all P <0.01). The less differentiated osteoblast phenotypes were significantly more chemosensitive at equimolar concentrations of methotrexate, vincristine, asparaginase, and dexamethasone than more differentiated phenotypes (all P <0.01). Furthermore, four agents significantly increased alkaline phosphatase (AP) activity in HOB cells. We conclude that individual chemotherapeutic agents added to osteoblast cell cultures reduce cell numbers, with osteoblast precursor cells being preferentially depleted. These results suggest that most of the agents may contribute to osteopenia in childhood malignancy by direct effects on cell numbers.
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PMID:In vitro effects of chemotherapeutic agents on human osteoblast-like cells. 1205 56

Silicon deficiency in animals leads to bone defects. This element may therefore play an important role in bone metabolism. Silicon is absorbed from the diet as orthosilicic acid and concentrations in plasma are 5-20 microM. The in vitro effects of orthosilicic acid (0-50 microM) on collagen type 1 synthesis was investigated using the human osteosarcoma cell line (MG-63), primary osteoblast-like cells derived from human bone marrow stromal cells, and an immortalized human early osteoblastic cell line (HCC1). Collagen type 1 mRNA expression and prolyl hydroxylase activity were also determined in the MG-63 cells. Alkaline phosphatase and osteocalcin (osteoblastic differentiation) were assessed both at the protein and the mRNA level in MG-63 cells treated with orthosilicic acid. Collagen type 1 synthesis increased in all treated cells at orthosilicic acid concentrations of 10 and 20 microM, although the effects were more marked in the clonal cell lines (MG-63, HCCl 1.75- and 1.8-fold, respectively, P < 0.001, compared to 1.45-fold in the primary cell lines). Treatment at 50 microM resulted in a smaller increase in collagen type 1 synthesis (MG-63 1.45-fold, P = 0.004). The effect of orthosilicic acid was abolished in the presence of prolyl hydroxylase inhibitors. No change in collagen type 1 mRNA level was seen in treated MG-63 cells. Alkaline phosphatase activity and osteocalcin were significantly increased (1.5, 1.2-fold at concentrations of 10 and 20 microM, respectively, P < 0.05). Gene expression of alkaline phosphatase and osteocalcin also increased significantly following treatment. In conclusion, orthosilicic acid at physiological concentrations stimulates collagen type 1 synthesis in human osteoblast-like cells and enhances osteoblastic differentiation.
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PMID:Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. 1263 84