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Suppressive effects of N-bisphosphonate in osteoblastic cells mitigated by non-N-bisphosphonate but not by sodium-dependent phosphate cotransporter inhibitor

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Title: Suppressive effects of N-bisphosphonate in osteoblastic cells mitigated by non-N-bisphosphonate but not by sodium-dependent phosphate cotransporter inhibitor
Authors: Baba, Tomomi T. / Miyazaki, Toshihiro / Ohara-Nemoto, Yuko / Nemoto, Takayuki K.
Issue Date: 22-Jul-2019
Publisher: John Wiley & Sons, Ltd.
Citation: Cell Biochemistry and Function, 37(6), pp.400-407; 2019
Abstract: There are two types of bisphosphonates (BPs), nitrogen-containing (N-BPs) and those free from nitrogen (non-N-BPs). Although N-BPs show greater inhibition of bone resorption than non-N-BPs, their effects are likely accompanied with inflammation, which non-N-BPs mitigate. We examined the competitive effects of zoledronate (ZOL), an N-BP, and etidronate (ETI), a non-N-BP, in osteoblasts. ZOL, but not ETI, markedly reduced alkaline phosphatase activity and cell viability in osteoblastic MC3T3-E1 and Saos2 cells, while that inhibition was relieved by simultaneous administration of ETI, possibly because of competition with ZOL for cellular uptake. However, phosphonoformate, an inhibitor of the phosphonate transporters SLC20A and SLC34A, did not mitigate the reducing effects of ZOL, suggesting that those transporters are not involved in BP uptake in osteoblastic cells. Additionally, ZOL reduced fibroblastic NIH3T3 and C3H10T1/2 cell viability, which was relieved by administration of both ETI and phosphonoformate. Transporter gene expression levels were significantly lower in osteoblasts as compared with fibroblasts, which may account for the distinct effects of phosphonoformate with different cell types. Together, our results suggest existence of a common uptake route of N-BPs and non-N-BPs into osteoblastic cells that is unrelated to the SLC20A and SLC34A families.
Keywords: bisphosphonate / cell differentiation / cell viability / etidronate / fibroblast / osteoblast / SLC transporter family / zoledronate
URI: http://hdl.handle.net/10069/39355
ISSN: 02636484
DOI: 10.1002/cbf.3418
Rights: © 2019 John Wiley & Sons, Ltd. / This is the peer reviewed version of the following article: Cell Biochemistry and Function, Article in Press, which has been published in final form at https://doi.org/10.1002/cbf.3418. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39355

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