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局部应用牙髓干细胞条件培养基预防大鼠拔牙窝药物相关性颌骨坏死的效果。

Effects of the prevention of medication-related osteonecrosis of the jaw by local administration of a dental pulp stem cell-conditioned medium to the rat tooth extraction socket.

机构信息

Course of Clinical Science, Field of Oral and Maxillofacial Surgery and Systemic Medicine, Oral and Maxillofacial Surgery, Graduate School of Life Dentistry At Niigata, The Nippon Dental University, 1-8 Hamaura-cho, Chuo-ku, Niigata, 951-8580, Japan.

Department of Oral and Maxillofacial Surgery, School of Life Dentistry At Niigata, The Nippon Dental University, 1-8 Hamaura-cho, Chuo-ku, Niigata, 951-8580, Japan.

出版信息

Odontology. 2021 Oct;109(4):836-844. doi: 10.1007/s10266-021-00607-2. Epub 2021 Apr 27.

DOI:10.1007/s10266-021-00607-2
PMID:33907964
Abstract

The onset of osteonecrosis of the jaw, which is a side effect of bisphosphonates, often develops after tooth extraction; measures for its prevention have not yet been established. While treatment with systemic administration of bone marrow stem cell-derived conditioned medium for medication-related osteonecrosis of the jaw (MRONJ) has been reported, its preventive effects have not been clarified yet, and the high degree of invasiveness of bone marrow fluid collection remains an issue. Therefore, we created a rat model of MRONJ using BP zoledronic acid, used a dental pulp stem cell-conditioned medium (DPSC-CM), which can be collected relatively easily, and locally applied it to the tooth extraction socket with atelocollagen and gelatin sponges. The preventive effect on the onset of MRONJ was subsequently examined. The results demonstrated that the bone exposure width of the extraction socket was reduced, and the mucosal covering was promoted in the atelocollagen + DPSC-CM group as compared with the other groups. Furthermore, histological results indicated a decrease in the number of empty bone lacunae, whereas immunohistochemical staining revealed the presence of many vascular endothelial growth factor (VEGF)-positive cells. Moreover, the results of the investigation of the sustained release of atelocollagen using VEGF indicated the release of VEGF over time. Our results suggest that local administration of DPSC-CM using atelocollagen may be a useful method for the prevention of MRONJ triggered by tooth extraction.

摘要

颌骨坏死的发病,这是双膦酸盐的一种副作用,通常在拔牙后发展;其预防措施尚未确定。虽然有报道称骨髓干细胞来源条件培养基治疗与药物相关的颌骨坏死 (MRONJ),但其预防效果尚不清楚,骨髓液采集的高度侵袭性仍然是一个问题。因此,我们使用唑来膦酸 BP 建立了 MRONJ 大鼠模型,使用相对容易采集的牙髓干细胞条件培养基 (DPSC-CM),并用纤维蛋白胶和明胶海绵将其局部应用于拔牙窝。随后检查了对 MRONJ 发病的预防作用。结果表明,与其他组相比,牙囊拔牙窝的骨暴露宽度减小,黏膜覆盖得到促进。此外,组织学结果表明空骨陷窝数量减少,而免疫组织化学染色显示存在许多血管内皮生长因子 (VEGF)阳性细胞。此外,使用 VEGF 对纤维蛋白胶的持续释放进行的研究表明 VEGF 随时间释放。我们的结果表明,使用纤维蛋白胶局部施用 DPSC-CM 可能是预防拔牙引发的 MRONJ 的一种有用方法。

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本文引用的文献

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Turk J Biol. 2020 Feb 17;44(1):34-47. doi: 10.3906/biy-1908-32. eCollection 2020.
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Bisphosphonate-related osteonecrosis. Application of adipose-derived stem cells in an experimental murine model.双膦酸盐相关性骨坏死。脂肪源性干细胞在实验性小鼠模型中的应用。
Med Oral Patol Oral Cir Bucal. 2019 Jul 1;24(4):e529-e536. doi: 10.4317/medoral.22959.
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Dental extraction following zoledronate, induces osteonecrosis in rat's jaw.
牙髓干细胞分泌因子对多种疾病的治疗潜力
Biomedicines. 2022 May 2;10(5):1049. doi: 10.3390/biomedicines10051049.
唑来膦酸治疗后拔牙会诱发大鼠颌骨坏死。
Med Oral Patol Oral Cir Bucal. 2017 Mar 1;22(2):e177-e184. doi: 10.4317/medoral.21609.