Journal of Dental Anesthesia and Pain Medicine

The Korean Dental Society of Anesthsiology (대한치과마취과학회)
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Propofol promotes osteoclastic bone resorption by increasing DC-STAMP expression

  • Kim, Eun-Jung (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Kim, Hyung Joon (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Baik, Seong Wan (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Kim, Kyung-Hoon (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Ryu, Sie Jeong (Department of Anesthesia and Pain Medicine, College of Medicine, Kosin University) ;
  • Kim, Cheul-Hong (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Shin, Sang-Wook (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University)
  • Received : 2018.11.23
  • Accepted : 2018.12.06
  • Published : 2018.12.31
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Abstract

Background: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to ${\alpha}$-tocopherol. It has been reported that ${\alpha}$-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs). Methods: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol ($0-50{\mu}M$) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion. Results: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP. Conclusion: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.

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References

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