神经肽Y与骨代谢研究进展

On the regulation of bone metabolism:A research review of neuropeptide Y

骨质疏松和骨折等骨代谢性疾病严重影响中老年人生活质量,是造成患者瘫痪和死亡的主要原因之一.成骨细胞和破骨细胞是机体维持骨稳态的关键细胞,其功能的失衡将引起骨代谢障碍.传统观点认为骨代谢调节主要受机体内分泌和机械力等作用的影响.但是近年来越来越多的证据表明神经系统包括中枢和外周在骨稳态维持中的重要性.神经肽Y(NPY)作为重要的神经肽,是连接神经系统和骨骼系统的重要桥梁.研究表明,NPY能够通过中枢途径和外周途径分别对机体骨代谢进行调控.骨表面和髓腔内的NPY能神经纤维以及成骨细胞、软骨细胞以及骨细胞表面的NPY受体为神经-骨代谢通路提供了基础.NPY能够直接作用于骨祖细胞,调节其向成骨细胞和破骨细胞的产生和分化.同时NPY作为机体能量代谢调节的关键分子,对于机体糖和脂肪等代谢也存在调控作用.动物模型研究进一步表明能量代谢可能直接或者间接参与骨稳态调节.因此,深入研究NPY与骨代谢的关系,阐明中枢与外周NPY调节骨代谢的机制将有助于进一步理解神经/内分泌-骨代谢轴,为未来骨代谢疾病的治疗提供新的思路.

Skeleton metabolic diseases such as osteoporosis and fracture have posed an detrimental impact on the elderly, which is a primary cause of paralysis and even death in patients. Osteoblast and osteoclast are the two major parts in the regulation of bone homeostasis and imbalance of these two cells, which may result in dysfunction of bone metabolism. Recent researches indicated that bone homeostasis was primarily regulated by endocrine, paracrine, and local mechanical processes. However, increasing evidences have indicated that the significant role of nerve system may involve in bone metabolism via both central and peripheral pathways. Neuropeptide Y(NPY), a neurotransmitter that belongs to a family of peptides,serves as a critical hinge connecting nerve system and skeleton system. Several studies have suggested that NPY generated by both central and peripheral nerve system could regulate bone homeostasis and that NPY-energic nerve fibers distributed on bone surface and in intramedullary cavity and NPY receptors located at osteoblast, chondrocyte, and osteocytes also provide a basis for nerve-skeleton metabolic pathways. NPY can directly regulate osteoprogenitor, involving in the production and differentiation of osteoblast and osteoclast. In addition, as a pivotal molecular of energy homeostasis, NPY may affect glucose and fat homeostasis. Studies of animal models also have further indicated energy metabolism may directly or indirectly participate in the regulation of bone mass. Therefore, further researches on the relationship between NPY and bone homeostasis may facilitate to unveil the central and peripheral regulatory effect of NPY on bone homeostasis and provide a new sight for the treatment of skeleton metabolism-related diseases in the future.