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Effects of chemotherapeutic agents on the function of primary human osteoblast-like cells derived from children

Effects of chemotherapeutic agents on the function of primary human osteoblast-like cells derived from children
Effects of chemotherapeutic agents on the function of primary human osteoblast-like cells derived from children
Studies in children treated with chemotherapy suggest that chemotherapeutic agents have deleterious effects on bone metabolism. We therefore evaluated the in vitro effects of clinically relevant concentrations of chemotherapeutic agents on the synthesis of type I collagen, alkaline phosphatase (AP) activity, and mineralization by primary human osteoblast-like (HOB) cells derived from children. Because serum 1,25-dihydroxyvitamin D(3) concentrations may be reduced during treatment with chemotherapy, the effect of chemotherapeutic agents on HOB cells cultured in the presence or absence of 1,25-dihydroxyvitamin D(3) was also evaluated. Type I collagen synthesis was reduced by all agents (P < 0.01) other than methotrexate, whereas the relative AP activity was increased (P < 0.01) by all agents. The relative number of cells staining intensely for AP after culture with agents increased (P < 0.05), and AP mRNA expression was increased (P < 0.01) with vincristine. 1,25-Dihydroxyvitamin D(3) ameliorated (P < 0.01) the depletion of HOB cell numbers by chemotherapeutic agents. Furthermore, vincristine and daunorubicin inhibited 1,25-dihydroxyvitamin D(3)-mediated AP activity (P < 0.01). We conclude that chemotherapeutic agents can adversely affect HOB cell function, and we speculate that this observation may account, in part, for the osteopenia observed during and after treatment of children with chemotherapy.
drug synergism, observation, genetics, male, agents, preschool, methotrexate, biosynthesis, research, cell count, pharmacology, daunorubicin, drug effects, activity, affect, culture, health, antagonists & inhibitors, osteoblasts, humans, human, in-vitro, expression, vincristine, bone, rna, cells, serum, antineoplastic agents, child, calcitriol, research support, treatment, collagen type i, messenger, minerals, physiology, adolescent, cultured, alkaline phosphatase, wales, collagen, metabolism, cytology, female
0021-972X
6088-6097
Davies, J.H.
9f18fcad-f488-4c72-ac23-c154995443a9
Evans, B.A.J.
d2b3bcf6-4387-4512-81b3-0509cb2d02ab
Jenney, M.E.M.
9c76c594-ec11-46e9-a0cb-1239b399c4d8
Gregory, J.W.
f14bbe24-2378-4a70-991d-4bbf8fa66ac5
Davies, J.H.
9f18fcad-f488-4c72-ac23-c154995443a9
Evans, B.A.J.
d2b3bcf6-4387-4512-81b3-0509cb2d02ab
Jenney, M.E.M.
9c76c594-ec11-46e9-a0cb-1239b399c4d8
Gregory, J.W.
f14bbe24-2378-4a70-991d-4bbf8fa66ac5

Davies, J.H., Evans, B.A.J., Jenney, M.E.M. and Gregory, J.W. (2003) Effects of chemotherapeutic agents on the function of primary human osteoblast-like cells derived from children. Journal of Clinical Endocrinology & Metabolism, 88 (12), 6088-6097. (doi:10.1210/jc.2003-030712).

Record type: Article

Abstract

Studies in children treated with chemotherapy suggest that chemotherapeutic agents have deleterious effects on bone metabolism. We therefore evaluated the in vitro effects of clinically relevant concentrations of chemotherapeutic agents on the synthesis of type I collagen, alkaline phosphatase (AP) activity, and mineralization by primary human osteoblast-like (HOB) cells derived from children. Because serum 1,25-dihydroxyvitamin D(3) concentrations may be reduced during treatment with chemotherapy, the effect of chemotherapeutic agents on HOB cells cultured in the presence or absence of 1,25-dihydroxyvitamin D(3) was also evaluated. Type I collagen synthesis was reduced by all agents (P < 0.01) other than methotrexate, whereas the relative AP activity was increased (P < 0.01) by all agents. The relative number of cells staining intensely for AP after culture with agents increased (P < 0.05), and AP mRNA expression was increased (P < 0.01) with vincristine. 1,25-Dihydroxyvitamin D(3) ameliorated (P < 0.01) the depletion of HOB cell numbers by chemotherapeutic agents. Furthermore, vincristine and daunorubicin inhibited 1,25-dihydroxyvitamin D(3)-mediated AP activity (P < 0.01). We conclude that chemotherapeutic agents can adversely affect HOB cell function, and we speculate that this observation may account, in part, for the osteopenia observed during and after treatment of children with chemotherapy.

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More information

Published date: December 2003
Keywords: drug synergism, observation, genetics, male, agents, preschool, methotrexate, biosynthesis, research, cell count, pharmacology, daunorubicin, drug effects, activity, affect, culture, health, antagonists & inhibitors, osteoblasts, humans, human, in-vitro, expression, vincristine, bone, rna, cells, serum, antineoplastic agents, child, calcitriol, research support, treatment, collagen type i, messenger, minerals, physiology, adolescent, cultured, alkaline phosphatase, wales, collagen, metabolism, cytology, female

Identifiers

Local EPrints ID: 59652
URI: https://eprints.soton.ac.uk/id/eprint/59652
ISSN: 0021-972X
PURE UUID: 708d03e3-89e8-46ba-a8eb-92811794dad8

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

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Contributors

Author: J.H. Davies
Author: B.A.J. Evans
Author: M.E.M. Jenney
Author: J.W. Gregory

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