Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada, Spain.
Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences. University of Granada, Spain.
Int J Med Sci. 2019 Oct 21;16(12):1534-1540. doi: 10.7150/ijms.36994. eCollection 2019.
The aim of this study was to elucidate the role of fibroblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ), evaluating the effect of zoledronate, alendronate, and ibandronate on the proliferation of fibroblasts and on their expression of genes essential for fibroblast physiology. Human CCD-1064Sk epithelial fibroblast cells were incubated in culture medium with 10, 10, or 10 M zoledronate, alendronate, or ibandronate. The proliferative capacity of fibroblasts was determined by spectrophotometry (MTT) at 24 of culture. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of BPs at a dose of 10 M on the expression of FGF, CTGF, TGF-β1, TGFβR1, TGFβR2, TGFβR3, DDR2, α-actin, fibronectin, decorin, and elastin. Fibroblasts proliferation was significantly increased at the lowest dose (10M) of each BP but was not affected at the higher doses (10 and 10M). The proliferation increase may be related to the rise in TGF-β1 and TGFβR1 expression detected after the treatment of cells with 10M of zoledronate, alendronate, or ibandronate. However, the expression of CTGF, DDR2, α-actin, fibronectin, and decorin decreased controls. The results of this study indicate that a very low BP dose (10 M) can significantly affect the physiology of fibroblasts, increasing their proliferative capacity and modulating the expression of multiple genes involved in their growth and differentiation.
这项研究的目的是阐明成纤维细胞在双膦酸盐相关性下颌骨骨坏死（BRONJ）中的作用，评估唑来膦酸、阿仑膦酸和伊班膦酸对成纤维细胞增殖及其对成纤维细胞生理学相关基因表达的影响。将人 CCD-1064Sk 上皮成纤维细胞在含有 10、10 或 10 M 唑来膦酸、阿仑膦酸或伊班膦酸的培养基中孵育。通过 24 小时培养的分光光度法（MTT）测定成纤维细胞的增殖能力。实时聚合酶链反应（RT-PCR）用于研究剂量为 10 M 的 BPs 对成纤维细胞中 FGF、CTGF、TGF-β1、TGFβR1、TGFβR2、TGFβR3、DDR2、α-肌动蛋白、纤连蛋白、饰胶蛋白聚糖和弹性蛋白表达的影响。每种 BP 的最低剂量（10M）均显著增加了成纤维细胞的增殖，但较高剂量（10 和 10M）则没有影响。增殖增加可能与用 10M 唑来膦酸、阿仑膦酸或伊班膦酸处理细胞后检测到的 TGF-β1 和 TGFβR1 表达升高有关。然而，CTGF、DDR2、α-肌动蛋白、纤连蛋白和饰胶蛋白聚糖的表达则低于对照组。本研究结果表明，非常低的 BP 剂量（10M）可显著影响成纤维细胞的生理学，增加其增殖能力，并调节其生长和分化相关的多个基因的表达。
