Inhibitory effects of Formononetin on CoCrMo particle-induced osteoclast activation and bone loss through downregulating NF-κB and MAPK signaling

Cell Signal. 2023 Jun:106:110651. doi: 10.1016/j.cellsig.2023.110651. Epub 2023 Mar 8.

Abstract

Wear particle-induced osteoclast over-activation is a major contributor to periprosthetic osteolysis and aseptic loosening, which can cause pathological bone loss and destruction. Hence, inhibiting excessive osteoclast-resorbing activity is an important strategy for preventing periprosthetic osteolysis. Formononetin (FMN) has been shown to have protective effects against osteoporosis, but no previous study has evaluated the effects of FMN on wear particle-induced osteolysis. In this study, we found that FMN alleviated CoCrMo alloy particles (CoPs)-induced bone loss in vivo and inhibited the formation and bone-resorptive function of osteoclasts in vitro. Moreover, we revealed that FMN exerted inhibitory effects on the expression of osteoclast-specific genes via the classical NF-κB and MAPK signaling pathways in vitro. Collectively, FMN is a potential therapeutic agent for the prevention and treatment of periprosthetic osteolysis and other osteolytic bone diseases.

Keywords: Aseptic loosening; Formononetin; MAPK; NF-κB; Osteoclast; Periprosthetic osteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption* / drug therapy
  • Bone Resorption* / pathology
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Osteoclasts / metabolism
  • Osteogenesis
  • Osteolysis* / drug therapy
  • RANK Ligand / metabolism
  • RANK Ligand / pharmacology

Substances

  • NF-kappa B
  • formononetin
  • RANK Ligand