Inhibition of KIF11 ameliorates osteoclastogenesis via regulating mTORC1-mediated NF-κB signaling

Biochem Pharmacol. 2023 Nov:217:115817. doi: 10.1016/j.bcp.2023.115817. Epub 2023 Sep 25.

Abstract

Osteoporosis, characterized by over-production and activation of osteoclasts, has become a major health problem especially in elderly women. In our study, we first tested the effect of Caudatin (Cau) in osteoclastogenesis, which is separated from Cynanchum auriculatum as a species of C-21 steroidal glyosides. The results indicated that Cau suppressed osteoclastogenesis in a time- and dose-dependent manner in vitro. Mechanistically, Cau was identified to inhibit NF-κB signaling pathway via modulation of KIF11-mediated mTORC1 activity. In vivo, by establishing an ovariectomized (OVX) mouse model to mimic osteoporosis, we confirmed that Cau treatment prevented OVX-induced bone loss in mice. In conclusion, we demonstrated that Cau inhibited NF-κB signaling pathway via modulation of KIF11-mediated mTORC1 activity to suppress osteoclast differentiation in vitro as well as OVX-induced bone loss in vivo. This provides the possibility of a novel prospective drug for osteoporosis remedies.

Keywords: Caudatin; KIF11; Osteoclastogenesis; Osteoporosis; RANKL; mTORC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption* / drug therapy
  • Bone Resorption* / metabolism
  • Bone Resorption* / prevention & control
  • Cell Differentiation
  • Kinesins / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • NF-kappa B / metabolism
  • Osteoclasts
  • Osteogenesis
  • Osteoporosis* / drug therapy
  • Osteoporosis* / metabolism
  • Osteoporosis* / prevention & control
  • Ovariectomy
  • RANK Ligand / pharmacology
  • Signal Transduction

Substances

  • Kinesins
  • NF-kappa B
  • RANK Ligand
  • Mechanistic Target of Rapamycin Complex 1
  • Kif11 protein, mouse