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双膦酸盐对口腔种植学的影响:阿仑膦酸钠和唑来膦酸增强了种植在钛上的牙龈成纤维细胞的基质金属蛋白酶的合成和活性。

Influence of bisphosphonates on oral implantology: Sodium alendronate and zoledronic acid enhance the synthesis and activity of matrix metalloproteinases by gingival fibroblasts seeded on titanium.

机构信息

Department of Dentistry, Ribeirão Preto University (UNAERP), Ribeirão Preto, SP, Brazil.

Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araraquara, SP, Brazil.

出版信息

Arch Oral Biol. 2021 Jul;127:105134. doi: 10.1016/j.archoralbio.2021.105134. Epub 2021 Apr 24.

DOI:10.1016/j.archoralbio.2021.105134
PMID:33962330
Abstract

OBJECTIVE

This study aimed to assess the influence of the bisphosphonates zoledronic acid and sodium alendronate on MMP-2 and MMP-9 synthesis and activity by gingival fibroblasts seeded onto titanium substrate.

DESIGN

Titanium discs were placed in 24-well cell culture plates and gingival fibroblasts were seeded (1 × 10 cells/discs) on them using Dulbecco's Modified Eagle's Medium (DMEM) + 10 % fetal bovine serum (FBS) for 24 h. After this period, a fresh serum-free DMEM containing zoledronic acid or sodium alendronate at 0.5 μM, 1 μM or 5 μM was applied on the cells for an additional of 24 h. Serum-free DMEM and tumor necrosis factor alpha (TNF-α) were used as negative and positive controls, respectively. MMP-2 and MMP-9 synthesis and activity were determined by ELISA (Enzyme-Linked Immunosorbent Assay) and conventional/in situ zymography. Quantitative data were analyzed by one-way ANOVA and Tukey's tests (α = 0.05). The in situ zymography data were qualitatively described.

RESULTS

Despite both bisphosphonates increased the MMPs synthesis, this effect was significant higher in zoledronic acid groups. MMPs activity resembled by gelatinolytic activity was also enhanced by sodium alendronate and zoledronic acid in a similar pattern.

CONCLUSIONS

Zoledronic acid and sodium alendronate increased in a dose-dependent manner MMP-2 and MMP-9 synthesis by gingival fibroblasts seeded on titanium. MMP-2 activity was up-regulated by zoledronic acid treatment.

摘要

目的

本研究旨在评估双膦酸盐唑来膦酸和阿仑膦酸钠对种植在钛基底上的牙龈成纤维细胞中 MMP-2 和 MMP-9 合成和活性的影响。

设计

将钛盘放置在 24 孔细胞培养板中,并用 Dulbecco 改良 Eagle 培养基(DMEM)+10%胎牛血清(FBS)将牙龈成纤维细胞(每盘 1×10 个细胞)接种于其上,孵育 24 小时。在此期间,将含有 0.5μM、1μM 或 5μM 唑来膦酸或阿仑膦酸钠的无血清 DMEM 新鲜应用于细胞上,再孵育 24 小时。无血清 DMEM 和肿瘤坏死因子-α(TNF-α)分别作为阴性和阳性对照。通过酶联免疫吸附测定(ELISA)和常规/原位酶谱法测定 MMP-2 和 MMP-9 的合成和活性。定量数据采用单因素方差分析和 Tukey 检验(α=0.05)进行分析。原位酶谱数据进行定性描述。

结果

尽管两种双膦酸盐均增加了 MMPs 的合成,但唑来膦酸组的这种作用更为显著。MMPs 活性通过明胶酶活性来反映,阿仑膦酸钠和唑来膦酸也以相似的方式增强。

结论

唑来膦酸和阿仑膦酸钠以剂量依赖的方式增加了种植在钛上的牙龈成纤维细胞中 MMP-2 和 MMP-9 的合成。唑来膦酸处理上调了 MMP-2 活性。

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