Isobavachalcone inhibits RANKL-induced osteoclastogenesis via miR-193-3p/NF-κB/NFATc1 signaling pathway in BMMs cells

Biosci Biotechnol Biochem. 2023 Aug 23;87(9):960-971. doi: 10.1093/bbb/zbad075.

Abstract

Inhibition of extensive osteoclastogenesis and bone resorption is considered a potential therapeutic target for the treatment of osteoporosis. Isobavachalcone (IBC) is derived from the traditional Chinese herb Psoralea corylifolia Linn. We showed that IBC dose-dependently suppressed receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis in bone marrow monocyte/macrophage (BMMs) and osteoclastic bone-resorption function without cytotoxicity at a dose of no more than 8 µmin vitro. Mechanistically, the results of western blot and quantitative real-time polymerase chain reaction (qRT-PCR) indicated that IBC inhibited the RANKL-induced degradation of IκBα and phosphorylation of nuclear factor kappa B (NF-κB) in BMMs, and subsequently downregulated the expression of osteoclastic-specific genes and osteoclastogenesis-related proteins. TRAP staining and qRT-PCR showed that IBC can inhibit osteoclast differentiation by down-regulating the expression of miR-193-3p on osteoclast differentiation. Overall, our findings suggest that IBC may serve as a promising compound for the treatment of osteoporosis and other metabolic bone diseases.

Keywords: NF-κB; RANKL; isobavachalcone; miR-193-3p; osteoclast.

MeSH terms

  • Bone Resorption* / drug therapy
  • Bone Resorption* / genetics
  • Bone Resorption* / metabolism
  • Cell Differentiation
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B / metabolism
  • NFATC Transcription Factors / metabolism
  • Osteoclasts
  • Osteogenesis
  • Osteoporosis* / metabolism
  • RANK Ligand / metabolism
  • RANK Ligand / pharmacology
  • Signal Transduction

Substances

  • NF-kappa B
  • isobavachalcone
  • RANK Ligand
  • MicroRNAs
  • NFATC Transcription Factors
  • MIRN193 microRNA, human