NPY revealed as a critical modulator of osteoblast function in vitro: New insights into the role of Y1 and Y2 receptors
NPY revealed as a critical modulator of osteoblast function in vitro: New insights into the role of Y1 and Y2 receptors
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DOI：
10.1002/jcb.22194
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发表时间：
2009-08
影响因子：
4
通讯作者：
Liliana Teixeira;D. Sousa;A. Nunes;M. Sousa;H. Herzog;M. Lamghari
中科院分区：
文献类型：
--
作者：
Liliana Teixeira;D. Sousa;A. Nunes;M. Sousa;H. Herzog;M. Lamghari
神经肽Y（NPY）最近已成为一个潜在的调节骨稳态。然而，NPY在成骨细胞活性中的作用和骨稳态中涉及NPY受体的生物学功能的相关性仍有待澄清。在这里，我们报告说，慢性升高的NPY水平导致调制的Y2受体的表达水平，标志着一个短暂的下调和上调，根据成骨细胞分化的阶段。我们还表明，NPY是一个负调节Y1受体的表达。药物激活Y2受体及其激动剂也产生类似的效应。功能分析还揭示了NPY的成骨潜力，成骨细胞表型标志物在NPY刺激的骨祖细胞中显著增强，可能是由于Y1受体的下调。相比之下，这些细胞表现出细胞外基质中钙沉积的减少，最有可能通过Y2受体信号传导介导。此外，我们发现，NPY调节核因子kB受体激活剂（NF-kB）（RANK）配体和骨保护素，这两个关键因素调节骨重建。具体而言，NPY抑制骨祖细胞中RANKL启动子的转录活性，并在分化早期增强成骨细胞中OPG的表达。而NPY对OPG的作用似乎与Y2受体的激活无关。综上所述，目前的数据支持通过直接作用于成骨细胞的骨稳态中的NPY通路的贡献。J.细胞。107：908-916，2009.© 2009 Wiley利斯公司
Neuropeptide Y (NPY) has recently emerged as a potential regulator of bone homeostasis. However, the relevance of NPY's role in osteoblast activity and the biological functions involving NPY receptors in bone homeostasis remain to be clarified. Here we report that chronically elevated NPY levels leaded to a modulation of the level of Y2 receptor expression marked with a transient down and upregulation according to the stage of osteoblast differentiation. We also show that NPY is a negative regulator of Y1 receptor expression. The pharmalogical activation of Y2 receptor with its agonist resulted in similar effect. Functional analysis also revealed the osteogenic potential of NPY with osteoblast phenotype markers being significantly enhanced in osteoprogenitor cells stimulated by NPY, probably due to the down‐regulation of Y1 receptor. In contrasts, these cells exhibit a reduction in calcium deposition in extracellular matrix most likely mediated via Y2 receptor signalling. Furthermore, we show that NPY modulates receptor activator of nuclear factor kB (NF‐kB) (RANK) ligand and osteoprotegerin, two key factors regulating bone remodelling. Specifically, NPY inhibits the transcriptional activity of RANKL promoter in osteoprogenitor cells and enhances OPG expression in osteoblasts at early stages of differentiation. However, NPY effect on OPG seemed to be unrelated to Y2 receptor activation. Taken together the present data supported the contribution of NPY pathway in bone homeostasis via a direct action on osteoblasts cells. J. Cell. Biochem. 107: 908–916, 2009. © 2009 Wiley‐Liss, Inc.