Low dose lithium supplementation activates Wnt/β-catenin signalling and increases bone OPG/RANKL ratio in mice

Biochem Biophys Res Commun. 2019 Apr 2;511(2):394-397. doi: 10.1016/j.bbrc.2019.02.066. Epub 2019 Feb 18.

Abstract

Lithium, a well-known inhibitor of glycogen synthase kinase-3β (GSK3β), can improve bone formation by activating the Wnt/β-catenin signalling pathway. However, most studies have used higher doses of lithium, which potentially have adverse effects. Herein, we report that low dose lithium supplementation (10 mg/kg/d for 6 weeks) in mice results in a serum lithium concentration of 0.02 mM significantly inhibiting GSK3β while activating Wnt/β-catenin in bone. In turn, we observed a significant increase in the expression of osteoprotegerin (OPG), with unaltered expression of nuclear-factor kβ ligand (RANKL), ultimately leading to a significant increase in the OPG/RANKL ratio. Altogether, our findings provide initial evidence that low dose lithium supplementation can promote the signalling pathways associated with bone formation.

Keywords: Bone turnover; Lithium; OPG and RANKL ratio; Wnt/β-catenin signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Lithium / administration & dosage
  • Lithium / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteogenesis / drug effects
  • Osteoprotegerin / metabolism*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • RANK Ligand / metabolism*
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / metabolism

Substances

  • Osteoprotegerin
  • Protein Kinase Inhibitors
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • beta Catenin
  • Lithium
  • Glycogen Synthase Kinase 3 beta