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

作者：Yuechun Chen, Zhen‐Yu Zhang, Huibo Ti, Jun‐Jie Wu, Feng‐Lai Yuan, Xia Li · 发表于：Journal of Orthopaedic Surgery and Research · 年份：2025 · DOI：10.1186/s13018-025-05944-4 · 被引用次数：4 · 研究领域：Axon Guidance and Neuronal Signaling、Nerve injury and regeneration、Nicotinic Acetylcholine Receptors Study

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, coincid...