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

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...

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Publicado en:Journal of Orthopaedic Surgery & Research Vol. 20; no. 1; pp. 1 - 16
Autores principales: Chen, Yuechun, Zhang, Zhenyu, Ti, Huibo, Wu, Junjie, Yuan, Feng-lai, Li, Xia
Formato: pictorial research tables/charts Journal Article
Publicado: BioMed Central 6/5/2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 6/5/2025
      vid: 20
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      pub: BioMed Central
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        10.1186/s13018-025-05944-4
        185724834
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        atl: Sympathetic cholinergic nerve fibres promote BMSC differentiation into osteoblasts via NRTN secretion: a potential treatment for osteoporosis.
      aug:
        au:
          Chen, Yuechun
          Zhang, Zhenyu
          Ti, Huibo
          Wu, Junjie
          Yuan, Feng-lai
          Li, Xia
        affil: https://ror.org/02ar02c28 Institute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, 343099, Wuxi, Jiangsu Province, China
      sug:
        subj:
          Osteoporosis Physiopathology
          Nerve Fibers Physiology
          Sympathetic Nervous System
          Nerve Growth Factors Metabolism
          Osteoblasts
          Mesenchymal Stem Cells
          Cell Differentiation
          Animal Studies
          Mice
          Models, Biological
          Polymerase Chain Reaction
          Comparative Studies
          Blotting, Western
          Enzyme-Linked Immunosorbent Assay
          Fluorescent Antibody Technique
          Staining and Labeling Methods
          In Vivo Studies
          Tomography, X-Ray Computed
          Immunohistochemistry
          In Vitro Studies
          Osteogenesis
          Funding Source
      ab: 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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