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Induction of tumor necrosis factor-α in Schwann cells after gradual elongation of rat sciatic nerve

  • Original article
  • Published:
Journal of Orthopaedic Science

Abstract

Background

Although limb lengthening has become a common treatment, the biochemical responses underlying the adaptation of elongated nerves are unclear. The purpose of this study was to clarify whether expression of cytokines and neurotrophins is altered in gradually elongated peripheral nerves.

Methods

Left sciatic nerves of adult rats were elongated by lengthening the femur up to 20 mm at a rate of 1, 2, or 20 mm/day. The ipsilateral and contralateral sciatic nerves of each group were resected 1, 4, 8, and 16 days after 20 mm of lengthening. mRNAs for interleukin-1β, interleukin-6, tumor necrosis factor-α (TNFα), nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 were semiquantified by reverse transcription-polymerase chain reaction. Histological changes were assessed by immunoperoxidase and immunofluorescence staining.

Results

Expression of TNFα mRNA was markedly induced in the ipsilateral sciatic nerves of the gradually elongated, 1 mm/day and 2 mm/day groups, although to a lesser extent than in the acutely elongated, 20 mm/day group. In contrast, mRNAs for other factors remained undetectable. The mRNA level for TNFα in each group was highest 1 day after 20 mm of lengthening. The highly up-regulated level in the acute group declined rapidly within 4 days and slowly thereafter; in contrast, the decrease in the gradual groups was always slow. Even 16 days later, the levels in all groups remained significantly elevated. Unexpectedly, TNFα mRNA expression was also induced in the contralateral side of all groups. Immunohistochemical staining showed that TNFα-immunoreactive cells in gradually elongated nerves were also positive for S-100 protein but negative for proliferating nuclear cell antigen, indicating that TNFα was produced by nonproliferating Schwann cells.

Conclusions

Gradual nerve elongation by limb lengthening induces production of TNFα in Schwann cells. Presumably, TNFα plays a critical role in the adaptation of peripheral nerves to elongation.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan

    Norio Hagiwara, Kazuo Ikeda & Katsuro Tomita

  2. Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Norio Hagiwara, Haruhiro Higashida & Shigeru Yokoyama

Authors
  1. Norio Hagiwara
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  4. Katsuro Tomita
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  5. Shigeru Yokoyama
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Hagiwara, N., Ikeda, K., Higashida, H. et al. Induction of tumor necrosis factor-α in Schwann cells after gradual elongation of rat sciatic nerve. J Orthop Sci 10, 614–621 (2005). https://doi.org/10.1007/s00776-005-0954-0

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  • DOI: https://doi.org/10.1007/s00776-005-0954-0

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