交感胆碱能神经纤维通过分泌神经营养因子促进骨髓间充质干细胞向成骨细胞分化：一种骨质疏松症的潜在治疗方法。

Sympathetic cholinergic nerve fibres promote BMSC differentiation into osteoblasts via NRTN secretion: a potential treatment for osteoporosis.

作者信息

Chen Yuechun, Zhang Zhenyu, Ti Huibo, Wu Junjie, Yuan Feng-Lai, Li Xia

机构信息

Institute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Wuxi, 343099, Jiangsu Province, China.

Department of Food Science and Engineering, Jiangnan University, Wuxi, 214028, Jiangsu Province, China.

出版信息

J Orthop Surg Res. 2025 Jun 5;20(1):571. doi: 10.1186/s13018-025-05944-4.

DOI:10.1186/s13018-025-05944-4

PMID:40474233

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12139376/

Abstract

BACKGROUND

Peripheral nerves within the bone actively participate in bone remodelling by secreting various bioactive molecules, and dysfunction or changes in their abundance greatly contribute to the onset of osteoporosis. While it is well established that sympathetic adrenergic nerve fibres reduce bone mass and contribute to osteoporosis, the role of sympathetic cholinergic signalling in this condition is still poorly understood. We aimed to investigate whether sympathetic cholinergic nerve fibres influence osteoporosis through the secretion of neurturin (NRTN).

METHODS

A mouse model of osteoporosis was established via bilateral ovariectomy (OVX). Differences in cholinergic signalling and NRTN expression levels between sham-operated control mice and OVX mice were assessed using methods such as quantitative real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. The effects of NRTN on bone mass and bone formation were examined in vivo through micro-computed tomography analysis, bone morphometric analysis, histological analysis, and immunohistochemistry staining. In vitro, clone formation assay, tartrate-resistant acid phosphatase staining, alkaline phosphatase staining, and alizarin red S staining were employed to validate the impacts of NRTN on osteoblast proliferation, osteoclast differentiation, and osteoblast differentiation.

RESULTS

Sympathetic cholinergic signalling was diminished in OVX mice, coinciding with a decrease in the neurotrophic factor, NRTN, which is secreted by sympathetic cholinergic nerve endings. NRTN treatment resulted in a dose-dependent increase in bone mass in OVX mice. Subsequent investigations confirmed that NRTN promotes bone formation in vivo and enhances the differentiation of bone marrow mesenchymal stem cells into osteoblasts in vitro.

CONCLUSIONS

Our results suggest that sympathetic cholinergic nerve fibres promote bone mass through NRTN secretion, providing new insights into potential therapeutic strategies for osteoporosis.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13018-025-05944-4.

摘要

背景

骨内的周围神经通过分泌多种生物活性分子积极参与骨重塑，其功能障碍或丰度变化在很大程度上导致骨质疏松症的发生。虽然交感肾上腺素能神经纤维减少骨量并导致骨质疏松症已得到充分证实，但交感胆碱能信号在这种情况下的作用仍知之甚少。我们旨在研究交感胆碱能神经纤维是否通过分泌神经营养因子（NRTN）影响骨质疏松症。

方法

通过双侧卵巢切除术（OVX）建立骨质疏松症小鼠模型。使用定量实时聚合酶链反应、蛋白质免疫印迹、酶联免疫吸附测定和免疫荧光染色等方法评估假手术对照小鼠和OVX小鼠之间胆碱能信号和NRTN表达水平的差异。通过微计算机断层扫描分析、骨形态计量分析、组织学分析和免疫组织化学染色在体内检查NRTN对骨量和骨形成的影响。在体外，采用克隆形成试验、抗酒石酸酸性磷酸酶染色、碱性磷酸酶染色和茜素红S染色来验证NRTN对成骨细胞增殖、破骨细胞分化和成骨细胞分化的影响。