Occlusal Trauma and Bisphosphonate-Related Osteonecrosis of the Jaw in Mice
Occlusal Trauma and Bisphosphonate-Related Osteonecrosis of the Jaw in Mice
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DOI：
10.1007/s00223-021-00916-2
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发表时间：
2021-09
影响因子：
4.2
通讯作者：
Y. Mine;Karin Okuda;Reina Yoshioka;Yuuki Sasaki;Tzu-Yu Peng;M. Kaku;Y. Yoshiko;H. Nikawa;Takeshi Murayama
中科院分区：
文献类型：
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作者：
Y. Mine;Karin Okuda;Reina Yoshioka;Yuuki Sasaki;Tzu-Yu Peng;M. Kaku;Y. Yoshiko;H. Nikawa;Takeshi Murayama
颌骨骨坏死（ONJ）是一种与抗骨吸收药物相关的严重不良事件，表现为颌面部骨暴露。先前的临床报告表明，机械创伤会以类似于拔牙的方式触发ONJ。据我们所知，很少有详细的病理生理学研究的机制，咬合/机械创伤影响ONJ。在这里，我们开发了一种新的小鼠模型，其在实验性过度咬合和含氮双膦酸盐（N-BP）治疗后表现出ONJ。该体内模型在牙槽骨，特别是下颌骨中显示ONJ。此外，实验性过度咬合诱导显著的牙槽骨吸收在小鼠下颌骨和上颌骨，而N-BP治疗完全防止牙槽骨吸收。在这项研究中，我们还模拟创伤暴露团块间充质干细胞（MSCs）/细胞外基质复合物的静水压力结合N-BP。静水压力负荷诱导从MSC分化的钙化细胞团释放乳酸脱氢酶（LDH）; N-BP引发增强LDH释放。这些体内和体外模型可能有助于进一步了解过度机械负荷对咬合创伤患者ONJ发作的影响。
Osteonecrosis of the jaw (ONJ) is a serious adverse event that is associated with antiresorptive agents, and it manifests as bone exposure in the maxillofacial region. Previous clinical reports suggest that mechanical trauma would trigger ONJ in a manner that is similar to tooth extractions. To the best of our knowledge, there have been few detailed pathophysiological investigations of the mechanisms by which occlusal/mechanical trauma influences ONJ. Here, we developed a novel mouse model that exhibits ONJ following experimental hyperocclusion and nitrogen-containing bisphosphonate (N-BP) treatment. This in vivo model exhibited ONJ in alveolar bone, particularly in the mandible. Moreover, the experimental hyperocclusion induced remarkable alveolar bone resorption in both mouse mandible and maxilla, whereas N-BP treatment completely prevented alveolar bone resorption. In this study, we also modeled trauma by exposing clumps of mesenchymal stem cells (MSCs)/extracellular matrix complex to hydrostatic pressure in combination with N-BP. Hydrostatic pressure loading induced lactate dehydrogenase (LDH) release by calcified cell clumps that were differentiated from MSCs; this LDH release was enhanced by N-BP priming. These in vivo and in vitro models may contribute further insights into the effect of excessive mechanical loading on ONJ onset in patients with occlusal trauma.