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Remifentanil Negatively Regulates RANKL-Induced Osteoclast Differentiation and Bone Resorption by Inhibiting c-Fos/NFATc1 Expression

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Remifentanil is commonly used in operating rooms and intensive care units for the purpose of anesthesia and sedation or analgesia. Although remifentanil may significantly affect the bone regeneration process in patients, there have been few studies to date on the effects of remifentanil on bone physiology. The purpose of this study was to investigate the effects of remifentanil on osteoclast differentiation and bone resorption. Bone marrow-derived macrophages (BMMs) were cultured for 4 days in remifentanil concentrations ranging from 0 to 100 ng/ml, macrophage colony-stimulating factor (M-CSF) alone, or in osteoclastogenic medium to induce the production of mature osteoclasts. To determine the degree of osteoclast maturity, tartrate-resistant acid phosphatase (TRAP) staining was performed. RT-PCR and western blotting analyses were used to determine the effect of remifentanil on the signaling pathways involved in osteoclast differentiation and maturation. Bone resorption and migration of BMMs were analyzed to determine the osteoclastic activity. Remifentanil reduced the number and size of osteoclasts and the formation of TRAP-positive multinuclear osteoclasts in a dose-dependent manner. Expression of c-Fos and NFATC1 was most strongly decreased in the presence of RANKL and remifentanil, and the activity of ERK was also inhibited by remifentanil. In the bone resorption assay, remifentanil reduced bone resorption and did not significantly affect cell migration. This study shows that remifentanil inhibits the differentiation and maturation of osteoclasts and reduces bone resorption.

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Authors and Affiliations

  1. Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Dental Research Institute, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Korea

    Ji-Young Yoon, Chul-Woo Baek & Eun-Jung Kim

  2. Department of Oral Physiology, School of Dentistry, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Korea

    Hyung-Joon Kim

  3. Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Korea

    Gyeong-Jo Byeon & Ji-Uk Yoon

  4. Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, 20, Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Korea

    Gyeong-Jo Byeon & Ji-Uk Yoon

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  1. Ji-Young Yoon
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  2. Chul-Woo Baek
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Correspondence to Ji-Uk Yoon.

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The authors have no financial conflicts of interest.

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Animal experiments were approved by the Committees on the Care and Use of Animals in Research at Pusan National University Dental Hospital (IACUC No. PNUDH-2016-032).

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Yoon, JY., Baek, CW., Kim, HJ. et al. Remifentanil Negatively Regulates RANKL-Induced Osteoclast Differentiation and Bone Resorption by Inhibiting c-Fos/NFATc1 Expression. Tissue Eng Regen Med 15, 333–340 (2018). https://doi.org/10.1007/s13770-018-0116-z

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  • DOI: https://doi.org/10.1007/s13770-018-0116-z

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