ArticleJournal of orthopaedic surgery and research2025
Sympathetic cholinergic nerve fibres promote BMSC differentiation into osteoblasts via NRTN secretion: a potential treatment for osteoporosis.
Article in Journal of orthopaedic surgery and research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Deciphering inter-organ communication: The multi-organ-bone axis in osteoporosis and emerging therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Sympathetic regulation of bone homeostasis and remodeling: molecular mechanisms, pathophysiological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Molecular mechanisms and therapeutic implications of the sympathetic nervous system in bone-related disorders: a brain-bone axis perspective.Bone research · 2025Review
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6 authors.
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Abstract
backgroundPeripheral 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).
methodsA 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.
resultsSympathetic 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.
conclusionsOur results suggest that sympathetic cholinergic nerve fibres promote bone mass through NRTN secretion, providing new insights into potential therapeutic strategies for osteoporosis.
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