骨源性因子ucOCN在运动抗抑郁中的作用机制

羧化不全骨钙素(ucOCN)是骨中成骨细胞分泌的特异性蛋白, 因其在调控神经发育、神经可塑性等中的重要角色而受到神经科学领域关注。“骨-脑”串联“对话”是骨内分泌-神经介导的应答系统, ucOCN透过血脑屏障后介导单胺类神经递质、神经内分泌、神经免疫、神经再生及基因表达等机制, 进而作用于海马CA3区、扣带回等脑区功能发挥来调节抑郁发生及改善。而ucOCN作为骨源性力学刺激敏感基因, 运动上调其表达后进入血液循环, 通过介导5-HT/GABA分泌、HPA轴功能、炎症反应、神经营养因子(BDNF等)表达或信号途径(如GSK3β/β-catenin、TLR4/miR-223/NLRP3等)激活等来实现“骨串联脑”, 发挥运动抗抑郁作用。通过对骨源性因子ucOCN介导脑区功能变化从而实现运动抗抑郁的作用机制进行探讨、梳理, 一方面有助于更深入了解骨内分泌功能, 另一方面为抑郁发生、改善和运动抗抑郁研究提供新的理论基础和研究思路。

The potential role of bone-derived factor ucOCN in the anti-depressive effects of exercise

Undercarboxylated osteocalcin(ucOCN)is a specific protein secreted by osteoblasts in bone.It has attracted attention in the field of neuroscience because of its important role in regulating neurodevelopment and neuroplasticity.“Bone-Brain Crosstalk”is a bone endocrine-nerve mediated response system.ucOCN modulate the monoamine neurotransmitters,neuroendocrine,neuroimmunity,nerve regeneration and gene expression after passing through the blood-brain barrier.ucOCN further acts on the hippocampus CA3 area,cingulate gyrus and other brain areas to regulate the occurrence and reduction of depression.As a bone-derived mechanical stimulation sensitive gene,ucOCN enters the blood circulation after exercise upregulating its expression,and mediates 5-HT/GABA secretion,HPA axis function,inflammation,neurotrophic factor(BDNF,etc.)expression or signal pathways(such as GSK3β/β-catenin,TLR4/miR-223/NLRP3,etc.)activation to achieve the“Bone-mediated brain”and mediate the antidepressant effect of exercise.This review emphasized the anti-depression effect of exercise through the discussion and sorting out of the mechanism of ucOCN-mediated brain function changes.On one hand,it is helpful to have a deeper understanding of bone endocrine function,on the other hand,it provides a new theoretical basis and research ideas for the occurrence and improvement of depression and the study of exercise anti-depression.