中枢神经肽Y（NPY）对骨代谢平衡具有重要的调控作用，而在骨组织细胞中发现NPY基因的表达提示非中枢的骨源性NPY的存在，但其对骨的作用尚不明确。申请人前期研究进一步证实在不同刺激条件下NPY在骨组织和骨细胞中存在差异表达，而且NPY可被骨组织细胞释放到细胞外液中，这启发我们深入NPY的功能探索并提出以下设想：骨源性NPY可能作为自分泌和/或旁分泌信号分子借助受体通路对骨组织及其细胞发挥局部调控作用。本项目拟进一步通过体内外实验，采用受体干预手段和小分子干扰（siRNA）等技术，旨在获得骨源性NPY/受体通路局部调控骨组织及其细胞的可靠证据，初步认识骨源性NPY、受体通路、细胞效应和组织反应的序列事件。本项目将阐明骨源性NPY通过受体介导对骨组织及其细胞的局部调控作用，为确立骨源性NPY为骨疾病治疗的新靶点提供科学依据。

There is increasing evidence for a contribution of the central neuropeptide Y (NPY) to the regulation of bone metabolism, but little attention was paid to the non-central osteogenic NPY which has been identified in bone cells. In our previous work, we have proved that the expression of NPY in bone and bone cells varies with the given stimulus conditions and bone cells themselves release NPY into the extracellular fluid, which enlighten us on the study about the actions of osteogenic NPY in bone. We conceive that osteogenic NPY acts as an autocrine and/or paracrine signalling molecule to regulate the bone and bone cells locally via its receptor. The purpose of the present research proposal is to obtain the reliable evidence for the local regulation of osteogenic NPY to bone and bone cells via its receptor by both in vitro and in vivo experiments using the receptor interventions and small interfering RNA (siRNA),and to get early insights into the relationships among these events including osteogenic NPY, receptor pathway, cellular biological effects and bone reaction. The present proposal will clarify the local actions of osteogenic NPY on bone and bone cells via the related receptor pathway. It is also expected to contribute to the development of a potential therapeutic target for bone diseases.