Anitua Eduardo, Zalduendo Mar, Troya María, Orive Gorka
Foundation Eduardo Anitua, Jacinto Quincoces, 39, 01007, Vitoria, Spain.
Laboratory of Regenerative Medicine, Biotechnology Institute (BTI), Vitoria, Spain.
Clin Oral Investig. 2016 Apr;20(3):513-21. doi: 10.1007/s00784-015-1528-y. Epub 2015 Jul 23.
Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common problem in patients undergoing long-term administration of highly potent nitrogen-containing bisphosphonates (N-BPs). This pathology occurs via bone and soft tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used to prevent bone loss in patients with bone dysfunction. The objective of this in vitro study was to evaluate the role of different ZA concentrations on the cells from human oral cavity, as well as the potential of plasma rich in growth factors (PRGF) to overcome the negative effects of this BP.
Primary human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell proliferation was evaluated by means of a fluorescence-based method. A colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to determine cell death, and the expression of both NF-κB and pNF-κB were quantified by Western blot analysis.
ZA had a cytotoxic effect on both human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell proliferation, stimulates apoptosis, and induces inflammation. However, the addition of PRGF suppresses all these negative effects of the ZA.
PRGF shows a cytoprotective role against the negative effects of ZA on primary oral cells.
At present, there is no definitive treatment for bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly palliatives. Our results revealed that PRGF has a cytoprotective role in cells exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the treatment of BRONJ pathology.
双膦酸盐相关颌骨坏死（BRONJ）是长期接受高效含氮双膦酸盐（N - BPs）治疗患者中的常见问题。这种病理情况通过骨骼和软组织机制发生。唑来膦酸（ZA）是用于预防骨功能障碍患者骨质流失的最强效静脉注射N - BP。本体外研究的目的是评估不同浓度ZA对人口腔细胞的作用，以及富含生长因子的血浆（PRGF）克服这种双膦酸盐负面影响的潜力。
使用原代人牙龈成纤维细胞和原代人牙槽骨成骨细胞。通过基于荧光的方法评估细胞增殖。使用比色法检测发生凋亡的DNA片段化以确定细胞死亡，并通过蛋白质印迹分析对NF - κB和pNF - κB的表达进行定量。
ZA对人牙龈成纤维细胞和人牙槽骨成骨细胞均有细胞毒性作用。这种双膦酸盐抑制细胞增殖，刺激凋亡并诱导炎症。然而，添加PRGF可抑制ZA的所有这些负面影响。
PRGF对ZA对原代口腔细胞的负面影响具有细胞保护作用。
目前，双膦酸盐相关颌骨坏死（BRONJ）尚无确切治疗方法，主要为姑息治疗。我们的结果表明，PRGF在暴露于唑来膦酸的细胞中具有细胞保护作用，从而为BRONJ病理的治疗提供了一种可靠的辅助治疗方法。
