Carnosol attenuates RANKL-induced osteoclastogenesis in vitro and LPS-induced bone loss

Int Immunopharmacol. 2020 Dec;89(Pt A):106978. doi: 10.1016/j.intimp.2020.106978. Epub 2020 Oct 8.

Abstract

Osteolysis is characterized by the imbalance of bone remodeling triggered by excessive activation of osteoclasts, which ultimately leads to pathological bone destruction. Diseases caused by overactive osteoclasts, such as osteolysis around the prosthesis, periodontitis and osteoporosis, are clinically common but lack effective treatment. Therefore, exploring regimens that could specifically impair the formation and function of osteoclasts has become a breakthrough in the treatment of these diseases. Carnosol is a natural phenolic diterpene with anti-inflammatory, antibacterial, anti-tumor and antioxidant properties. In this study, we found that carnosol can impede RANKL-induced osteoclastogenesis via modulating the activation of NF-κb and JNK signaling pathways in vitro. Additionally, we confirmed that carnosol could alleviate bone loss in amurine model of LPS-induced inflammatory bone erosion in vivo. Thence, these findings demonstrate that carnosol may be a potentially effective regent for the treatment of osteoclast-related disorders.

Keywords: Carnosol; NFATc1; Osteoclast; RANKL.

MeSH terms

  • Abietanes / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bone Remodeling / drug effects*
  • Disease Models, Animal
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis / drug effects*
  • Osteolysis / chemically induced
  • Osteolysis / metabolism
  • Osteolysis / pathology
  • Osteolysis / prevention & control*
  • Phosphorylation
  • RANK Ligand / pharmacology*
  • RAW 264.7 Cells
  • Signal Transduction

Substances

  • Abietanes
  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • NF-kappa B
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • carnosol
  • JNK Mitogen-Activated Protein Kinases