Skeletal unloading induces osteoblast apoptosis and targets α5β1-PI3K-Bcl-2 signaling in rat bone
Skeletal unloading induces osteoblast apoptosis and targets α5β1-PI3K-Bcl-2 signaling in rat bone
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DOI：
10.1016/j.yexcr.2006.10.021
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发表时间：
2007-01-15
影响因子：
3.7
通讯作者：
Marie, P. J.
中科院分区：
文献类型：
--
作者：
Dufour, C.;Holy, X.;Marie, P. J.
废用导致成骨细胞发生改变和骨丢失的机制尚不完全清楚。采用大鼠尾部悬吊模型，研究骨骼去负荷对成骨细胞及骨细胞凋亡的影响。尾部悬吊2 ~ 7 d可导致胫骨骨量减少，并诱导成骨细胞早期凋亡丢失和骨细胞延迟凋亡丢失。肾上腺重量和血浆皮质酮水平没有显着差异，在加载和卸载大鼠在任何时间点，表明成骨细胞/骨细胞凋亡发生独立的内源性糖皮质激素。废用诱导成骨细胞/骨细胞凋亡的机制基础进行了检查。我们发现，α 5 β 1整合素和磷酸化磷脂酰肌醇-3激酶（p-PI 3 K）蛋白水平在未加载的干骺端长骨与加载的骨相比短暂降低。相反，p-FAK和p-ERK p42/44水平没有显著改变。有趣的是，未加载长骨中p-PI 3 K水平的降低与存活蛋白Bcl-2水平的降低相关，Bax水平不变，导致Bax/Bcl-2水平增加。结果表明，大鼠骨骼卸载诱导糖皮质激素非依赖性的成骨细胞凋亡的立即增加，与大鼠骨中α 5 β 1-PI 3 K-Bcl-2存活通路的减少相关，这可能有助于改变成骨细胞的发生和卸载诱导的骨质减少。(c)2006年爱思唯尔公司All rights reserved.
The mechanisms underlying the altered osteoblastogenesis and bone loss in response to disuse are incompletely understood. Using the rat tail suspension model, we studied the effect of skeletal unloading on osteoblast and osteocyte apoptosis. Tail suspension for 2 to 7 days decreased tibial bone mass and induced early apoptotic loss of osteoblasts and delayed apoptotic loss of osteocytes. Surrenal gland weight and plasma corticosterone levels did not differ in loaded and unloaded rats at any time point, indicating that osteoblast/osteocyte apoptosis occurred independently of endogenous glucocorticoids. The mechanistic basis for the disuse-induced osteoblast/osteocyte apoptosis was examined. We found that alpha 5 beta 1 integrin and phosphorylated phosphatidyl-inositol-3 kinase (p-PI3K) protein levels were transiently decreased in unloaded metaphyseal long bone compared to loaded bones. In contrast, p-FAK and p-ERK p42/44 levels were not significantly altered. Interestingly, the reduced p-PI3K levels in unloaded long bone was associated with decreased levels of the survival protein Bcl-2 with unaltered Bax levels, causing increased Bax/Bcl-2 levels. The results indicate that skeletal unloading in rats induces a glucocorticoid-independent, immediate increase in osteoblast apoptosis associated with decreased alpha 5 beta 1-PI3K-Bcl-2 survival pathway in rat bone, which may contribute to the altered osteoblastogenesis and osteopenia induced by unloading. (c) 2006 Elsevier Inc. All rights reserved.