Propofol attenuates osteoclastogenesis by lowering RANKL/OPG ratio in mouse osteoblasts

Int J Med Sci. 2018 May 14;15(7):723-729. doi: 10.7150/ijms.22713. eCollection 2018.

Abstract

Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis.

Keywords: Bone remodeling; OPG; Osteoblast; Propofol; RANKL.

MeSH terms

  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Bone Remodeling
  • Cell Differentiation
  • Glycoproteins
  • Mice
  • Osteoblasts
  • Osteoclasts
  • Osteogenesis / drug effects*
  • Osteoprotegerin / drug effects
  • Osteoprotegerin / metabolism*
  • Propofol / pharmacology*
  • RANK Ligand / drug effects
  • RANK Ligand / metabolism*

Substances

  • Anesthetics, Intravenous
  • Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Propofol