ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Bone Research
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1580230
Augmentation of bone formation by sympathectomy in rats as evaluated by [ 99m Tc]Tc-MDP
Provisionally accepted- 1Fujian Medical University, Fuzhou, China
- 2Orthopedic Department, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- 3Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- 4Fujian Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, Fuzhou, China
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The role of the sympathetic nervous system in bone metabolism remains unclear.Given that 99m Tc-methylene diphosphonate ([ 99m Tc]Tc-MDP) uptake reflects active bone formation and mineralization, this study aims to investigate the effects of sympathetic denervation on bone formation in rats using [ 99m Tc]Tc-MDP SPECT/CT imaging.Twenty rats were randomly assigned to a superior cervical ganglionectomy (SCGx) group (n = 10) or a sham-operated control group (n = 10). Circular cranial fractures were surgically created in both groups. Micro SPECT/CT imaging was performed at 3, 6, and 9 weeks postoperatively to assess bone mineral density (BMD), bone volume/tissue volume (BV/TV), and bone volume (BV). In a separate experiment, 12 additional rats underwent either bilateral lumbar sympathectomy (n = 6) or sham operation (n = 6). At 9 weeks, [ 99m Tc]Tc-MDP biodistribution in harvested bone tissues was measured. Immunohistochemical staining for tyrosine hydroxylase (TH) and Ki67 was used to evaluate sympathetic innervation and cell proliferation in craniums, while immunofluorescence co-labeling for Ki67 and osteopontin (OPN) identified proliferating osteoblasts. In vitro, MC3T3-E1 osteoblasts were treated with norepinephrine (NE) or control medium for 24 hours. Cell proliferation was assessed using EdU staining. Additionally, sympathetic neurons isolated from neonatal rats were co-cultured with MC3T3-E1 cells in Transwell systems, and mineralization and alkaline phosphatase (ALP) activity were evaluated.Results: Successful SCGx was confirmed by signs of Horner's syndrome. SCGx rats exhibited significantly higher [ 99m Tc]Tc-MDP uptake and increased BMD, BV/TV, and BV in peri-fracture regions at all time points (p < 0.0001). Lumbar sympathectomy increased tracer uptake in femurs, tibias, lumbar vertebrae, and sacra (p < 0.01), but not in cervical or thoracic vertebrae. TH expression decreased, while Ki67 and OPN levels increased in SCGx craniums. NE suppressed MC3T3-E1 proliferation (p < 0.0001), and co-culture with sympathetic neurons reduced mineralization and ALP activity (both p < 0.0001).Sympathectomy can enhance osteoblast prolifeation and augment bone formation, which can be effectively assessed and quantified using [ 99m Tc]Tc-MDP SPECT/CT imaging.
Keywords: Bone formation, Sympathectomy, [ 99m Tc]Tc-MDP, SPECT/CT imaging, Rats
Received: 20 Feb 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Cai, Lin, Zhuang, Miao and Yun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuehong Zhuang, Orthopedic Department, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
Weibing Miao, Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
Xie Yun, Orthopedic Department, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
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