This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davies, J. H. Articles by Gregory, J. W. Search for Related Content PubMed PubMed Citation Articles by Davies, J. H. Articles by Gregory, J. W.

Effects of Chemotherapeutic Agents on the Function of Primary Human Osteoblast-Like Cells Derived from Children

Department of Child Health (J.H.D., B.A.J.E., J.W.G.), University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom; and Department of Paediatric Oncology (M.E.M.J.), Llandough Hospital, Cardiff CF64 2XX, United Kingdom

Address all correspondence and requests for reprints to: Dr. J. H. Davies, Lecturer in Child Health, Department of Child Health, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom. E-mail: daviesjh{at}cf.ac.uk.

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 D₃ 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 D₃ 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 D₃ ameliorated (P < 0.01) the depletion of HOB cell numbers by chemotherapeutic agents. Furthermore, vincristine and daunorubicin inhibited 1,25-dihydroxyvitamin D₃-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.

This work was supported by LATCH (Llandough Hospital aims to treat children with cancer with hope), Llandough Hospital, Penarth, Cardiff CF64 2XX, United Kingdom and Novo Nordisk.

Abbreviations: AP, Alkaline phosphatase; CICP, C-terminal propeptide of type I collagen; HOB, human osteoblast-like.

This article has been cited by other articles:

				J. Tan, P. P. Dwivedi, P. Anderson, B. K. Nutchey, P. O'Loughlin, H. A. Morris, B. K. May, A. Ferrante, and C. S. Hii Antineoplastic agents target the 25-hydroxyvitamin D3 24-hydroxylase messenger RNA for degradation: implications in anticancer activity Mol. Cancer Ther., December 1, 2007; 6(12): 3131 - 3138. [Abstract] [Full Text] [PDF]