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Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue

Bisphosphonates (BPs) are anti-resorptive agents commonly used to treat bone-related diseases; however, soft tissue-related side-effects are frequently reported in some BP users, such as oral or gastrointestinal (GI) ulcerations. BPs are stable analogs of pyrophosphate and have high affinity to hydr...

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Autores principales: BAE, SUSAN, SUN, SHUTING, AGHALOO, TARA, OH, JU-EUN, McKENNA, CHARLES E., KANG, MO K., SHIN, KI-HYUK, TETRADIS, SOTIRIOS, PARK, NO-HEE, KIM, REUBEN H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094592/
https://www.ncbi.nlm.nih.gov/pubmed/24920042
http://dx.doi.org/10.3892/ijmm.2014.1802
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author BAE, SUSAN
SUN, SHUTING
AGHALOO, TARA
OH, JU-EUN
McKENNA, CHARLES E.
KANG, MO K.
SHIN, KI-HYUK
TETRADIS, SOTIRIOS
PARK, NO-HEE
KIM, REUBEN H.
author_facet BAE, SUSAN
SUN, SHUTING
AGHALOO, TARA
OH, JU-EUN
McKENNA, CHARLES E.
KANG, MO K.
SHIN, KI-HYUK
TETRADIS, SOTIRIOS
PARK, NO-HEE
KIM, REUBEN H.
author_sort BAE, SUSAN
collection PubMed
description Bisphosphonates (BPs) are anti-resorptive agents commonly used to treat bone-related diseases; however, soft tissue-related side-effects are frequently reported in some BP users, such as oral or gastrointestinal (GI) ulcerations. BPs are stable analogs of pyrophosphate and have high affinity to hydroxyapatite, allowing them to bind to the bone surfaces and exert suppressive effects on osteoclast functions. However, the underlying mechanisms as to how bone-seeking BPs also exert cytotoxic effects on soft tissue remain unknown. In the present study, we investigated the localization of nitrogen-containing BPs (N-BPs) in hard and soft tissue using fluorescently-labeled N-BPs in vitro. We developed osteomucosal tissue constructs in vitro to recapitulate the hard and soft tissue of the oral cavity. A histological examination of the osteomucosal tissue constructs revealed a differentiated epithelium over the bone containing osteocytes and the periosteum, similar to that observed in the rat palatal tissues. Following treatment with the fluorescently-labeled bisphosphonate, AF647-ZOL, the osteomucosal constructs exhibited fluorescent signals, not only in the bone, but also in the epithelium. No fluorescent signals were observed from the control- or ZOL-treated constructs, as expected. Collectively, the data from the present study suggest that N-BPs localize to epithelial tissue and that such a localization and subsequent toxicity of N-BPs may be associated, at least in part, with soft tissue-related side-effects.
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spelling pubmed-40945922014-07-14 Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue BAE, SUSAN SUN, SHUTING AGHALOO, TARA OH, JU-EUN McKENNA, CHARLES E. KANG, MO K. SHIN, KI-HYUK TETRADIS, SOTIRIOS PARK, NO-HEE KIM, REUBEN H. Int J Mol Med Articles Bisphosphonates (BPs) are anti-resorptive agents commonly used to treat bone-related diseases; however, soft tissue-related side-effects are frequently reported in some BP users, such as oral or gastrointestinal (GI) ulcerations. BPs are stable analogs of pyrophosphate and have high affinity to hydroxyapatite, allowing them to bind to the bone surfaces and exert suppressive effects on osteoclast functions. However, the underlying mechanisms as to how bone-seeking BPs also exert cytotoxic effects on soft tissue remain unknown. In the present study, we investigated the localization of nitrogen-containing BPs (N-BPs) in hard and soft tissue using fluorescently-labeled N-BPs in vitro. We developed osteomucosal tissue constructs in vitro to recapitulate the hard and soft tissue of the oral cavity. A histological examination of the osteomucosal tissue constructs revealed a differentiated epithelium over the bone containing osteocytes and the periosteum, similar to that observed in the rat palatal tissues. Following treatment with the fluorescently-labeled bisphosphonate, AF647-ZOL, the osteomucosal constructs exhibited fluorescent signals, not only in the bone, but also in the epithelium. No fluorescent signals were observed from the control- or ZOL-treated constructs, as expected. Collectively, the data from the present study suggest that N-BPs localize to epithelial tissue and that such a localization and subsequent toxicity of N-BPs may be associated, at least in part, with soft tissue-related side-effects. D.A. Spandidos 2014-08 2014-06-11 /pmc/articles/PMC4094592/ /pubmed/24920042 http://dx.doi.org/10.3892/ijmm.2014.1802 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
BAE, SUSAN
SUN, SHUTING
AGHALOO, TARA
OH, JU-EUN
McKENNA, CHARLES E.
KANG, MO K.
SHIN, KI-HYUK
TETRADIS, SOTIRIOS
PARK, NO-HEE
KIM, REUBEN H.
Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
title Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
title_full Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
title_fullStr Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
title_full_unstemmed Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
title_short Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
title_sort development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094592/
https://www.ncbi.nlm.nih.gov/pubmed/24920042
http://dx.doi.org/10.3892/ijmm.2014.1802
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