Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study
Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study
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瘦素通过成骨细胞骨代谢的多种方式促进骨化：一项初步研究
DOI：
10.3109/09513590.2013.798278
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发表时间：
2013-08-01
影响因子：
2
通讯作者：
Xu, Wenming
中科院分区：
文献类型：
--
作者：
Zhang, Jing;Li, Tingting;Xu, Wenming
摘要瘦素可能是预防绝经后妇女骨质疏松症的一种潜在选择。本研究的目的是探讨瘦素对成骨细胞骨代谢影响的分子机制。从成年雌性大鼠顶骨分离原代成骨细胞。siRNA抑制成骨细胞OB-Rb mRNA水平，阻断瘦素信号传导。利用基因芯片检测全基因组表达，初步探讨瘦素调控成骨细胞活性的分子机制。siRNA的最佳浓度为25 nM，对OB-Rb mRNA的抑制作用最大。通过抑制瘦素信号传导，骨化（p < 0.05）和骨矿化（p = 0.0001）下调，而骨吸收（p = 0.007），成骨细胞分化（p = 0.026）和骨重建的负调节（p = 0.004）上调。OB-Rb siRNA可调控部分基因的表达。碱性磷酸酶（p = 0.014）和骨钙素（p = 0.002）的表达减少，而血管内皮生长因子A（p = 0.0076）和IL-6（p = 0.021）的表达增加。在成骨细胞模型中，瘦素通过多种途径促进成骨，包括骨矿化、骨重建、骨吸收和成骨细胞分化，但具体哪种途径起关键作用尚待进一步研究。
Abstract Leptin may be a potential option in preventing osteoporosis for menopausal women. The objective of this study is to explore the molecular mechanism of leptin on bone metabolism in osteoblast. Primary osteoblasts were isolated from parietal bone of adult female rats. mRNA level of OB-Rb in osteoblasts was inhibited by siRNA to block leptin signal transmission. The whole genome expression was tested by using gene chip to preliminarily explore the molecular mechanism of leptin in regulating osteoblast activity. The optimal concentration of siRNA was 25 nM, resulting in a maximal inhibition of OB-Rb mRNA. Ossification (p < 0.05) and bone mineralization (p = 0.0001) were downregulated by inhibiting leptin signal transmission, while bone resorption (p = 0.007), osteoblast differentiation (p = 0.026) and negative regulation of bone remodeling (p = 0.004) were upregulated. The expressions of some genes were regulated by OB-Rb siRNA. The expressions of alkaline phosphatase (p = 0.014) and osteocalcin (p = 0.002) were reduced, while that of vascular endothelial growth factor A (p = 0.0076) and IL-6 (p = 0.021) were increased. In a model of osteoblast, leptin positively promotes ossification through multiple ways including bone mineralization, remodeling, resorption and osteoblast differentiation, but which way plays the most critical role is not discussed in this study and needs to be clarified in future.