Phytol Suppresses Osteoclast Differentiation and Oxidative Stress through Nrf2/HO-1 Regulation in RANKL-Induced RAW264.7 Cells

Cells. 2022 Nov 14;11(22):3596. doi: 10.3390/cells11223596.

Abstract

Osteoporosis is a systemic skeletal disorder where osteoclasts are prevalent among osteoblasts. Oxidative stress is one of the main causes of osteoporosis, and nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses. Phytol, a diterpene isolated from Stevia rebaudiana leaves, has many biological effects, including antimicrobial, antioxidant, and anti-inflammatory effects. This study investigated the crosstalk between Nrf2 and osteoclast differentiation in the presence of phytol. Phytol inhibited osteoclast differentiation through TRAP-positive and F-actin formation. The expression of anti-nuclear factor of activated T cells-c1 (NFATc1) and c-Fos was suppressed by phytol, as shown using Western blot and RT-PCR analysis. Phytol inhibited oxidative stress by suppressing reactive oxidant species (ROS) accumulation while recovering antioxidant enzymes, including superoxide dismutase and catalase. Additionally, phytol ameliorated osteoclast-specific differentiation, function, and oxidative stress through Nrf2 regulation by siRNA transfection. In conclusion, these data demonstrate the inhibitory effect of phytol on osteoclast differentiation through Nrf2 regulation, suggesting its potential use in oxidative stress-related osteoporosis and bone diseases.

Keywords: Nrf2; osteoclast; oxidative stress; phytol; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Mice
  • NF-E2-Related Factor 2* / metabolism
  • Osteoclasts / metabolism
  • Osteoporosis* / metabolism
  • Oxidative Stress
  • Phytol / metabolism
  • Phytol / pharmacology
  • RAW 264.7 Cells

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Phytol

Grants and funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2019R1A5A2027340 and 2021R1A2C2007937). This work was also supported by the Korea Environment Industry & Technology Institute (KEITI) through a project to improve the development of multi-ministerial national biological research resources, funded by the Republic of Korea Ministry of Environment (MOE) (grant number 2021003420003).