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硼酸盐生物活性玻璃通过恢复成骨和血管生成来预防唑来膦酸诱导的颌骨坏死。

Borate bioactive glass prevents zoledronate-induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis.

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Oral Dis. 2020 Nov;26(8):1706-1717. doi: 10.1111/odi.13436. Epub 2020 Jun 16.

Abstract

OBJECTIVES

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of systemic nitrogen-containing bisphosphonate (N-BP) administration, which leads to osteonecrosis, pain, and infection. Despite much effort, effective remedies are yet to be established. This study aimed to investigate potential recovery effect of borate bioactive glass (BBG) in vitro and in vivo.

METHODS

The effect of BBG on zoledronate-treated bone marrow mesenchymal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored by cell counting kit-8, EdU assay, flow cytometry, alkaline phosphatase staining, alizarin red staining, angiogenesis experiment, and real-time quantitative polymerase chain reaction. The preventive effect of BBG on zoledronate-induced osteonecrosis of the jaw in rat model was examined by micro-CT, HE staining, and immunohistochemistry.

RESULTS

Exposure of BBG to BMSCs and HUVECs increased cell proliferation and restored their osteogenesis and angiogenesis potential in vitro. The BRONJ lesions were satisfactorily repaired and bone mineral density, bone volume/tissue volume, trabecula number, OCN-positive cells, and CD31-positive cells were increased in the BBG-treated groups compared with saline-treated groups.

CONCLUSIONS

Exposure of BMSCs and HUVECs to BBG restores osteogenesis and angiogenesis inhibited by zoledronate. BBG successfully restores extraction socket healing of BRONJ in rat model.

摘要

目的

颌骨骨坏死(BRONJ)是一种严重的并发症,由全身含氮双膦酸盐(N-BP)给药引起,导致骨坏死、疼痛和感染。尽管进行了大量努力,但仍未建立有效的治疗方法。本研究旨在研究硼酸盐生物活性玻璃(BBG)在体外和体内的潜在恢复效果。

方法

通过细胞计数试剂盒-8、EdU 测定、流式细胞术、碱性磷酸酶染色、茜素红染色、血管生成实验和实时定量聚合酶链反应,研究 BBG 对唑来膦酸盐处理的骨髓间充质细胞(BMSCs)和人脐静脉内皮细胞(HUVECs)的影响。通过 micro-CT、HE 染色和免疫组织化学检查 BBG 对唑来膦酸盐诱导的大鼠颌骨骨坏死模型的预防作用。

结果

BBG 暴露于 BMSCs 和 HUVECs 可增加细胞增殖,并在体外恢复其成骨和血管生成潜力。与生理盐水组相比,BBG 治疗组的 BRONJ 病变得到了满意的修复,骨矿物质密度、骨体积/组织体积、小梁数、OCN 阳性细胞和 CD31 阳性细胞增加。

结论

BBG 暴露于 BMSCs 和 HUVECs 可恢复唑来膦酸盐抑制的成骨和血管生成。BBG 成功恢复了 BRONJ 大鼠模型拔牙窝愈合。

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