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In vitro effects of chemotherapeutic agents on human osteoblast-like cells

In vitro effects of chemotherapeutic agents on human osteoblast-like cells
In vitro effects of chemotherapeutic agents on human osteoblast-like cells
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.
childhood, drug therapy, vincristine, cell differentiation, culture, methods, agents, pharmacology, treatment, wales, child, health, osteoblasts, human, metabolism, affect, cell count, in vitro, etoposide, cell line, research, cell culture techniques, metabolic, combination, asparaginase, differentiation, in-vitro, research support, bone, drug effects, cytology, phenotype, bone diseases, alkaline phosphatase, humans, activity, dexamethasone, methotrexate
0171-967X
408-415
Davies, J.H.
9f18fcad-f488-4c72-ac23-c154995443a9
Evans, B.A.
2679ef85-28bc-4ee9-8c3f-8550d40e5f63
Jenney, M.E.
4aa4993c-7f3f-4662-8f52-d084d67a1540
Gregory, J.W.
f14bbe24-2378-4a70-991d-4bbf8fa66ac5
Davies, J.H.
9f18fcad-f488-4c72-ac23-c154995443a9
Evans, B.A.
2679ef85-28bc-4ee9-8c3f-8550d40e5f63
Jenney, M.E.
4aa4993c-7f3f-4662-8f52-d084d67a1540
Gregory, J.W.
f14bbe24-2378-4a70-991d-4bbf8fa66ac5

Davies, J.H., Evans, B.A., Jenney, M.E. and Gregory, J.W. (2002) In vitro effects of chemotherapeutic agents on human osteoblast-like cells. Calcified Tissue International, 70 (5), 408-415. (doi:10.1007/s002230020039).

Record type: Article

Abstract

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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More information

Published date: May 2002
Keywords: childhood, drug therapy, vincristine, cell differentiation, culture, methods, agents, pharmacology, treatment, wales, child, health, osteoblasts, human, metabolism, affect, cell count, in vitro, etoposide, cell line, research, cell culture techniques, metabolic, combination, asparaginase, differentiation, in-vitro, research support, bone, drug effects, cytology, phenotype, bone diseases, alkaline phosphatase, humans, activity, dexamethasone, methotrexate

Identifiers

Local EPrints ID: 59651
URI: http://eprints.soton.ac.uk/id/eprint/59651
ISSN: 0171-967X
PURE UUID: 55f80c54-926f-4d23-b5b6-1385a28c11e5

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Date deposited: 04 Sep 2008
Last modified: 13 Mar 2019 20:30

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