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https://hdl.handle.net/2440/43975
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Type: | Journal article |
Title: | Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects |
Author: | Xian, C. Cool, J. Scherer, M. Pyragius, C. Fan, C. Covino, M. Foster, B. |
Citation: | Bone, 2007; 41(5):842-850 |
Publisher: | Elsevier Science Inc |
Issue Date: | 2007 |
ISSN: | 8756-3282 1873-2763 |
Statement of Responsibility: | Cory J. Xian, Johanna C. Cool, Michaela A. Scherer, Carmen E. Macsai, Chiaming Fan, Mark Covino and Bruce K. Foster |
Abstract: | Methotrexate (MTX) is a commonly used anti-metabolite in childhood oncology and is known to cause bone growth arrest and osteoporosis; yet the underlying mechanisms for MTX-induced bone growth defects remain largely unclear. This study characterized damaging effects in young rats of acute chemotherapy with 5 once-daily doses of MTX (0.75 mg/kg) on the cellular activities in the growth plate in producing calcified cartilage and trabecular bone and on activities of osteoblastic cells in the metaphysis. MTX treatment significantly induced chondrocyte apoptosis. MTX also suppressed chondrocyte proliferation and reduced collagen-II mRNA expression and total thickness of the growth plate, with the damage being most obvious on day 9 after the first injection, and with the growth plate histological structure returning normal on day 14. In the adjacent metaphyseal bone, mirroring the decrease in the width of the growth plate, production of primary spongiosa bone was markedly reduced and bone volume of the secondary spongiosa was decreased. Furthermore, MTX treatment significantly induced osteocyte apoptosis in the primary spongiosa and reduced proliferation of osteoblasts and preosteoblasts particularly in the secondary spongiosa. These observations suggest that methotrexate chemotherapy may cause bone growth defects by arresting cellular activities in the growth plate in producing calcified cartilage and primary trabecular bone and by decreasing pools of metaphyseal osteoblastic cells. However, this short-term MTX treatment only caused transit suppressions on growth plate cartilage and trabecular bone, as most cellular and histological parameters had recovered by day 14 or 21. |
Keywords: | Growth Plate Animals Rats Rats, Sprague-Dawley Methotrexate Antimetabolites, Antineoplastic Apoptosis Bone Development Male |
Description: | Crown copyright © 2007 Published by Elsevier Inc. |
DOI: | 10.1016/j.bone.2007.07.021 |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/525233/description#description |
Published version: | http://dx.doi.org/10.1016/j.bone.2007.07.021 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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