G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis
G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis
复制标题
G-CSF/SCF 通过抗细胞凋亡对患有类固醇相关性骨坏死的兔子发挥有益作用。
DOI：
10.1016/j.yexmp.2012.06.003
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发表时间：
2013-02-01
影响因子：
3.6
通讯作者：
Liu, Xianzhe
中科院分区：
文献类型：
--
作者：
Wu, Xinghuo;Yang, Shuhua;Liu, Xianzhe
目的：骨坏死又称无血管性坏死，骨坏死的发病机制包括两种类型的细胞死亡：坏死和凋亡。股骨头坏死中的细胞凋亡被认为是糖皮质激素诱导的皮质骨丢失的关键决定因素。本研究旨在探讨粒细胞集落刺激因子和干细胞因子（G-CSF/SCF）对兔激素性骨坏死的抗凋亡作用。方法：采用低剂量脂多糖和脉冲大剂量甲基强的松龙诱导骨坏死的方法。预防药物组分别给予100 μ g/kg/d g - csf和25 μ g/kg/d SCF。采用血液学和组织形态学方法观察骨坏死的治疗效果。细胞凋亡通过定量TUNEL染色、活化caspase-3免疫染色和免疫印迹检测。结果：G-CSF/SCF处理能增加血清骨钙素分泌，抑制血清抗酒石酸酸性磷酸酶（TRAP5b）表达。预防组骨坏死发生率明显低于类固醇组（42.1%对88.2%）。组织形态学分析显示，G-CSF/SCF预处理能够提高骨小梁矿物质堆积率（MAR）和骨形成率（BFR）。定量TUNEL和活化caspase-3水平显示预防组细胞凋亡较低。结论：G-CSF/SCF处理可抑制兔模型骨细胞caspase-3依赖性凋亡，对预防激素性ON有有益作用。(C) 2012爱思唯尔公司版权所有。
Objectives: Osteonecrosis is also known as avascular necrosis, and two types of cell death are included in the pathogenesis of osteonecrosis: necrosis and apoptosis. Apoptosis in the osteonecrosis of femoral head is thought to be the key determinant of glucocorticoid-induced cortical bone loss. The present study was implemented to evaluate the anti-apoptotic effect of Granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF) in rabbits with steroid-induced osteonecrosis.Methods: In the experiment, osteonecrosis was induced by low-dose lipopolysaccharide and subsequent pulsed high-dose methylprednisolone. Rabbits in preventive medicine group were treated with100 mu g/kg/d G-CSF and 25 mu g/kg/d SCF. Then hematological and histomorphometric methods were used to investigate the treatment effects of osteonecrosis. Apoptosis was assessed via quantitative TUNEL staining and activated caspase-3 immunostaining and immunoblotting.Results: The results showed that G-CSF/SCF treatment could increase the secretion of serum osteocalcin, but inhibit the expression of serum tartrate-resistant acid phosphatase (TRAP5b). The incidence of osteonecrosis was significantly decreased in Preventive group when compared with Steroid group (42.1% vs. 88.2%). Histomorphometric analysis showed that G-CSF/SCF pre-disposal treatment was able to increase trabecular mineral appositional rate (MAR) and bone formation rate (BFR). Quantitative TUNEL and activated caspase-3 levels showed lower apoptosis in the Preventive group.Conclusions: In conclusion, G-CSF/SCF treatment could inhibit caspase-3-dependent apoptosis in osteocytes to exert beneficial effects in preventing steroid-induced ON in rabbit models. (C) 2012 Elsevier Inc. All rights reserved.