Remifentanil negatively regulates RANKL-induced osteoclast differentiation and bone resorption by inhibiting c-Fos/NFATc1 expression
Open accessAbstract
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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Remifentanil promoted the differentiation of murine pre-osteoclasts and induced their maturation in one experimental setting, although the exact opposite effects, namely reduction of the number and size of osteoclasts and formation of tartrate-resistant acid phosphatase-positive multinuclear osteoclasts by remifentanil, have also been described.
“In this vein, remifentanil promoted the differentiation of murine pre-osteoclasts and induced their maturation in one experimental setting (220), although the exact opposite effects, namely reduction of the number and size of osteoclasts and the formation of tartrate-resistant acid phosphatase-positive multinuclear osteoclasts by remifentanil, have also been described (221).”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [221]
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References 25 · Cited by 17
Research works printed but not linked: 1
- [12]12. Matziolis G, Rau HM, Klever P, Erli HJ, Paar O. Modification of human osteoblasts by various analgesics. Unfallchirurg. 2002;105:527-31.
- Authors
- Yoon, J.-Y., Baek, C.-W., Kim, H.-J., Kim, E.-J., Byeon, G.-J., & Yoon, J.-U.
- Affiliations
- Pusan National University Dental Hospital (KR)
- Pusan National University (KR)
- Pusan National University Yangsan Hospital (KR)
- Corresponding author
- Yoon, Ji-Young
- Yoon, Ji-Uk
- Venue
- Tissue Engineering and Regenerative Medicine
- Published
- 2018-04-21
- Volume
- 15
- Issue
- 3
- Pages
- 333-340
- ISSN
- 1738-2696 (ISSN-L)
- 2212-5469
- PMC
- PMC6171682
- OpenAlex
- W2799334837
- Cited by
- 17
- References
- 25
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 2
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Tissue Engineering and Regenerative Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Japanese Society of Anesthesiologists
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- remifentanil, osteoclastogenesis, bone resorption, RANKL, c-fos, NFATc1, ERK signaling, bone marrow-derived macrophages, osteoclast migration, bone physiology
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