骨骼源性因子调控认知功能的机制研究

Research progress on the mechanism of regulation of cognitive function with bone-derived factors

骨骼源性因子,也称骨骼因子(osteokine),是主要由骨组织细胞分泌的生物活性因子和多肽。既往研究表明,骨骼源性因子可作用于胰腺、脂肪和肝脏等组织或器官,参与调节能量代谢,从而在糖尿病等代谢性疾病的病理生理学中发挥重要调控作用。近年研究证实,骨钙素、成纤维细胞生长因子23、dickkopf相关蛋白1、骨硬化蛋白和脂质运载蛋白2等因子经血液循环,可能进入大脑,通过促进单胺类神经递质的合成代谢以及脑源性神经营养因子表达、促使神经发生、提高突触可塑性、增强神经元自噬以及维持脑内离子代谢和微环境稳态等,进而调控认知功能。深入探讨骨骼源性因子与大脑之间潜在的生物学联系,能够有助于进一步筛选延缓老年人认知功能下降的靶向药物,并为制定老年人脑健康促进的干预方案开拓新思路。

Bone-derived factors,also known as osteokine,are bioactive factors and peptides mainly secreted by bone tissue cells.Previous studies have shown that bone-derived factors act on pancreas,fat,liver,and other tissues or organs,participate in the regulation of organism energy metabolism,and thus play an important regulatory role in the pathophysiology of metabolic diseases such as diabetes.Recent studies have confirmed that bone-derived factors such as osteocalcin,fibroblast growth factor 23,dickkopf-related protein 1,sclerosin,and lipocalin 2,among others,may enter the brain through blood circulation,and regulate cognitive function via promoting the anabolism of monoamine neurotransmitters and the expression of brain-derived neurotrophic factor,inducing neurogenesis,improving synaptic plasticity,enhancing neuronal autophagy,and maintaining ion metabolism and microenvironment homeostasis.In-depth exploring the potentially biological link between bone-derived factors and brain may help to further screen targeted drugs to delay the decline of cognitive function,and to open up new ideas for formulating intervention programs to promote brain health in the elderly.