TY - JOUR
T1 - Occlusal Trauma and Bisphosphonate-Related Osteonecrosis of the Jaw in Mice
AU - Mine, Yuichi
AU - Okuda, Karin
AU - Yoshioka, Reina
AU - Sasaki, Yuuki
AU - Peng, Tzu Yu
AU - Kaku, Masato
AU - Yoshiko, Yuji
AU - Nikawa, Hiroki
AU - Murayama, Takeshi
N1 - Funding Information:
This study was partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Y.M. [17K17181 and 20K18604].
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - 3D culture
KW - Bisphosphonate
KW - Hydrostatic pressure
KW - Hyperocclusive state
KW - Occlusal trauma
KW - Osteonecrosis of the jaw
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U2 - 10.1007/s00223-021-00916-2
DO - 10.1007/s00223-021-00916-2
M3 - Article
AN - SCOPUS:85115784000
SN - 0171-967X
VL - 110
SP - 380
EP - 392
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 3
ER -