Department of Pharmacology, Pharmacognosy and Botany, Complutense University, 28040 Madrid, Spain.
SALURIS, 28040 Madrid, Spain.
Int J Mol Sci. 2021 Sep 22;22(19):10195. doi: 10.3390/ijms221910195.
Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0-700 μM). Colostrum co-treated with DEX was executed at 0.1-5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.
糖皮质激素诱导性骨质疏松症(GIO)是最常见的继发性骨质疏松症之一。GIO 部分是由于成骨细胞和破骨细胞的凋亡。此外,大剂量的地塞米松(DEX),一种合成的糖皮质激素受体激动剂,通过启动炎症过程导致神经细胞凋亡而引发神经退行性变。在这里,研究了一种具有神经保护作用的牛初乳,以研究其在糖皮质激素处理的 MC3T3-E1 成骨细胞中对抗糖皮质激素诱导的神经元损伤的抗凋亡活性。通过将 MC3T3-E1 细胞暴露于 DEX(0-700 μM)来建立凋亡性成骨细胞模型。牛初乳与 DEX 共同处理的浓度为 0.1-5.0 mg/mL。测量所有治疗方案的细胞活力。评估 caspase-3 激活以确定 DEX 暴露下成骨细胞凋亡及其被牛初乳共同处理的潜在预防作用。测量还原型谷胱甘肽(GSH)以确定牛初乳共同处理是否减轻 DEX 介导的氧化应激驱动的细胞凋亡。进行 Western blot 以确定 DEX 或 DEX 加牛初乳暴露后 p-ERK1/2、Bcl-XL、Bax 和 Hsp70 蛋白的水平。牛初乳可防止 DEX 暴露引起的细胞活力下降、caspase-3 激活增加和氧化应激。与 DEX 共同处理的细胞表现出更高水平的 p-ERK1/2 和更低水平的 Bcl-XL、Bax 和 Hsp70。我们的数据支持这样的观点,即牛初乳可能能够通过激活 ERK 途径和调节 Hsp70 系统来减少 DEX 诱导的细胞凋亡。我们提供了初步证据,说明牛初乳作为一种复杂的多成分乳制品,除了其神经保护作用外,还可能影响经历凋亡的成骨细胞的存活。