Bone-specific overexpression of NPY modulates osteogenesis.
Bone-specific overexpression of NPY modulates osteogenesis.
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发表时间：
2012-12
影响因子：
1.9
通讯作者：
I. Matić;B. Matthews;Tomislav Kizivat;J. Igwe;I. Marijanović;S. Ruohonen;E. Savontaus;D. Adams;I. Kalajzic
中科院分区：
文献类型：
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作者：
I. Matić;B. Matthews;Tomislav Kizivat;J. Igwe;I. Marijanović;S. Ruohonen;E. Savontaus;D. Adams;I. Kalajzic
神经肽Y（NPY）是一种参与调节食欲和能量稳态的肽。遗传数据表明，NPY通过中枢和外周活动减少骨形成。神经肽Y是由各种类型的细胞，包括骨细胞和成骨细胞产生的，有证据表明，外周神经肽Y是重要的骨形成的调节。我们试图研究骨源性神经肽Y在骨代谢中的作用。方法建立一种NPY在成熟成骨细胞和骨细胞中特异性过表达的小鼠（Col2.3NPY），并在体内和体外表征这些小鼠的骨表型。结果3月龄动物的松质骨和皮质骨体积减少，但骨形成率和破骨细胞活性无明显变化。来自Col2.3NPY小鼠的颅骨成骨细胞培养物也显示矿化减少和成骨标记基因的表达。结论：成骨细胞/骨细胞源性神经肽Y能够改变体内和体外骨形成，可能是神经肽Y调节骨形成的重要来源。然而，可能的是，其他外周来源的NPY，如交感神经系统和脉管系统也有助于外周调节骨转换。
OBJECTIVES Neuropeptide Y (NPY) is a peptide involved in the regulation of appetite and energy homeostasis. Genetic data indicates that NPY decreases bone formation via central and peripheral activities. NPY is produced by various cell types including osteocytes and osteoblasts and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. We sought to investigate the role of bone-derived NPY in bone metabolism. METHODS We generated a mouse where NPY was over-expressed specifically in mature osteoblasts and osteocytes (Col2.3NPY) and characterized the bone phenotype of these mice in vivo and in vitro. RESULTS Trabecular and cortical bone volume was reduced in 3-month-old animals, however bone formation rate and osteoclast activity were not significantly changed. Calvarial osteoblast cultures from Col2.3NPY mice also showed reduced mineralization and expression of osteogenic marker genes. CONCLUSIONS Our data suggest that osteoblast/osteocyte-derived NPY is capable of altering osteogenesis in vivo and in vitro and may represent an important source of NPY for regulation of bone formation. However, it is possible that other peripheral sources of NPY such as the sympathetic nervous system and vasculature also contribute to peripheral regulation of bone turnover.