Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue.
Development of oral osteomucosal tissue constructs in vitro and localization of fluorescently-labeled bisphosphonates to hard and soft tissue.
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DOI：
10.3892/ijmm.2014.1802
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发表时间：
2014-08
影响因子：
5.4
通讯作者：
Kim RH
中科院分区：
文献类型：
--
作者：
Bae S;Sun S;Aghaloo T;Oh JE;McKenna CE;Kang MK;Shin KH;Tetradis S;Park NH;Kim RH
双膦酸盐 (BP) 是抗骨吸收剂，常用于治疗骨相关疾病；然而，一些 BP 使用者经常报告与软组织相关的副作用，例如口腔或胃肠道 (GI) 溃疡。 BP 是焦磷酸盐的稳定类似物，与羟基磷灰石具有高亲和力，使其能够与骨表面结合并对破骨细胞功能产生抑制作用。然而，寻骨BP如何对软组织发挥细胞毒性作用的潜在机制仍不清楚。在本研究中，我们利用荧光标记的 N-BP 在体外研究了含氮 BP (N-BP) 在硬组织和软组织中的定位。我们在体外开发了骨粘膜组织结构，以重现口腔的硬组织和软组织。骨粘膜组织结构的组织学检查揭示了含有骨细胞和骨膜的骨骼上的分化上皮，类似于在大鼠腭组织中观察到的情况。用荧光标记的双膦酸盐 AF647-ZOL 处理后，骨粘膜结构不仅在骨中而且在上皮中都表现出荧光信号。正如预期的那样，在对照或 ZOL 处理的构建体中没有观察到荧光信号。总的来说，本研究的数据表明，N-BP 定位于上皮组织，并且 N-BP 的这种定位和随后的毒性可能至少部分与软组织相关副作用相关。
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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影响因子：
6.2
作者：
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通讯作者：
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作者：
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