感觉神经通过分泌肽基脯氨酰顺反异构酶 D(Cyp40)直接促进破骨细胞生成

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Junqin Li, Bin Liu, Hao Wu, Shuaishuai Zhang, Zhuowen Liang, Shuo Guo, Huijie Jiang, Yue Song, Xing Lei, Yi Gao, Pengzhen Cheng, Donglin Li, Jimeng Wang, Yang Liu, Di Wang, Nazhi Zhan, Jing Xu, Lin Wang, Guozhi Xiao, Liu Yang, GuoXian Pei
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引用次数: 0

摘要

由于感觉神经具有传入功能,最近发现它还能产生传出效应,直接改变器官的生理机能。此外,一些研究强调了感觉神经在调节破骨细胞生理功能中间接但关键的作用。然而,关于感觉神经传出对破骨细胞的直接影响还缺乏证据。在本研究中,我们发现高水平的传出信号直接从感觉神经传入破骨细胞。此外,感觉过敏会明显增加破骨细胞的骨吸收,感觉神经元(SNs)会在体外共培养系统中直接促进破骨细胞的生成。此外,我们还利用相对和绝对定量异位标签(iTRAQ)筛选了一种新型神经肽--Cyp40。我们观察到,Cyp40是来自感觉神经的传出信号,它通过芳基烃受体(AhR)-Ras/Raf-p-Erk-NFATc1途径在破骨细胞生成过程中发挥关键作用。这些发现揭示了感觉神经影响骨调节的新机制,即通过分泌Cyp40直接促进破骨细胞生成。因此,抑制Cyp40可作为改善骨质疏松症患者骨质量和促进骨损伤后骨修复的一种策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40)

Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40)

Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.

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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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