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

  • Authors:
    • Susan Bae
    • Shuting Sun
    • Tara Aghaloo
    • Ju-Eun Oh
    • Charles E. McKenna
    • Mo K. Kang
    • Ki-Hyuk Shin
    • Sotirios Tetradis
    • No-Hee Park
    • Reuben H. Kim
  • View Affiliations

  • Published online on: June 11, 2014     https://doi.org/10.3892/ijmm.2014.1802
  • Pages: 559-563
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Abstract

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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August-2014
Volume 34 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Bae S, Sun S, Aghaloo T, Oh J, McKenna CE, Kang MK, Shin K, Tetradis S, Park N, Kim RH, Kim RH, et al: Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue. Int J Mol Med 34: 559-563, 2014
APA
Bae, S., Sun, S., Aghaloo, T., Oh, J., McKenna, C.E., Kang, M.K. ... Kim, R.H. (2014). Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue. International Journal of Molecular Medicine, 34, 559-563. https://doi.org/10.3892/ijmm.2014.1802
MLA
Bae, S., Sun, S., Aghaloo, T., Oh, J., McKenna, C. E., Kang, M. K., Shin, K., Tetradis, S., Park, N., Kim, R. H."Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue". International Journal of Molecular Medicine 34.2 (2014): 559-563.
Chicago
Bae, S., Sun, S., Aghaloo, T., Oh, J., McKenna, C. E., Kang, M. K., Shin, K., Tetradis, S., Park, N., Kim, R. H."Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue". International Journal of Molecular Medicine 34, no. 2 (2014): 559-563. https://doi.org/10.3892/ijmm.2014.1802