Abstract：
Medication-related osteonecrosis of the jaw (MRONJ) is an intractable adverse event. Dental implants are one of the triggering factors of MRONJ, and implant therapy with low MRONJ risk is required. This study aimed to investigate a rat model of MRONJ induced by extraoral placement of titanium materials and the use of mesenchymal stromal cell (MSCs) sheets to prevent MRONJ. Eight-week-old male rats were administered zoledronate and dexamethasone thrice weekly until killing. A week after drug initiation, a titanium screw and a plate were placed on the left buccal side of the mandible. Allogeneic bone marrow-derived MSC sheets were co-grafted with the titanium plates in the MSC sheet ( +) group. Six weeks after titanium placement, the rats were killed, and their excised mandibular bones were subjected to micro-computed tomography (CT) analysis. Histological analysis was performed after the titanium implants were removed. Empty lacunae visualized on hematoxylin and eosin staining were used as evidence of bone necrosis. Bone necrosis was reduced in the MSC sheet ( +) group. Tartrate-resistant acid phosphatase (TRAP) staining revealed a decreased number of TRAP-positive cells in areas with a large number of empty lacunae in the MSC sheet (-) group. Micro-CT analyses demonstrated that the bone volume fraction (BV/TV) was not significantly different between the MSC sheet (-) and ( +) groups. We conclude that MRONJ can be triggered by a titanium placement in rats, and grafting of allogeneic MSC sheets has the potential to prevent MRONJ.
摘要：
药物相关的颌骨坏死（MRONJ）是一种棘手的不良事件。牙种植体是MRONJ的触发因素之一，并且需要具有低MRONJ风险的植入治疗。本研究旨在研究经口外放置钛材料诱导的MRONJ大鼠模型，并使用间充质基质细胞（MSCs）片预防MRONJ。八周大的雄性大鼠每周三次给予唑来膦酸和地塞米松直至杀死。开始用药一周后，钛螺钉和板被放置在下颌骨的左颊侧。同种异体骨髓衍生的MSC片与MSC片(+)组中的钛板共接枝。钛放置六周后，老鼠被杀了，并对切除的下颌骨进行显微计算机断层扫描（CT）分析。在取出钛植入物后进行组织学分析。在苏木精和伊红染色上可见的空腔被用作骨坏死的证据。在MSC片(+)组中,骨坏死减少。抗酒石酸酸性磷酸酶（TRAP）染色显示，MSC片（-）组中有大量空腔区的TRAP阳性细胞数量减少。Micro-CT分析表明,骨体积分数(BV/TV)在MSC片(-)和(+)组之间没有显著差异。我们得出的结论是，MRONJ可以通过在大鼠中放置钛来触发，同种异体MSC片的嫁接有可能防止MRONJ。
