Nuciferine prevents bone loss by disrupting multinucleated osteoclast formation and promoting type H vessel formation

FASEB J. 2020 Mar;34(3):4798-4811. doi: 10.1096/fj.201902551R. Epub 2020 Feb 10.

Abstract

Recently, type H vessels were reported to couple angiogenesis and osteogenesis during osteoclastogenesis, and tartrate-resistant acid phosphatase (Trap)+ preosteoclasts were found to secrete increased PDGF-BB to promote type H vessel formation. Therefore, utilization of type H vessels may be a strategy to treat diseases involving bone loss. In the present study, we found that nuciferine, a natural bioactive compound, has various effects, including inhibiting osteoclastogenesis and promoting type H vessel formation. Nuciferine inhibited osteoclastogenesis and bone resorption but increased the relative number of Trap+ preosteoclasts. Nuciferine restrained the expression of osteoclast-specific genes and proteins, promoted PDGF-BB production and potentiated related angiogenic activities by inhibiting the MAPK and NF-κB signaling pathways in vitro. We confirmed the bone-protective effects of nuciferine in ovariectomized mice and found that nuciferine treatment increased the PDGF-BB concentration and the number of type H vessels in the femur. In conclusion, our results demonstrated that nuciferine can decrease multinucleated osteoclast formation and promote type H vessel formation through preservation of Trap+ preosteoclasts via inhibition of the MAPK and NF-κB signaling pathways and may be an excellent agent for the treatment of diseases involving bone loss.

Keywords: CD31; Emcn; PDGF-BB; preosteoclast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aporphines / therapeutic use*
  • Becaplermin / metabolism
  • Blotting, Western
  • Bone Resorption / metabolism*
  • Bone Resorption / prevention & control*
  • Cell Survival / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects*
  • Osteogenesis / drug effects
  • RANK Ligand / pharmacology
  • Real-Time Polymerase Chain Reaction
  • Wound Healing / drug effects

Substances

  • Aporphines
  • NF-kappa B
  • RANK Ligand
  • Becaplermin
  • nuciferine