Fructus Ligustri Lucidi preserves bone quality through induction of canonical Wnt/β-catenin signaling pathway in ovariectomized rats

Phytother Res. 2021 Jan;35(1):424-441. doi: 10.1002/ptr.6817. Epub 2020 Aug 4.

Abstract

Fructus Ligustri Lucidi (FLL) has been preclinically and clinically used to treat musculoskeletal diseases. However, whether and how FLL affect the canonical Wnt/β-catenin signaling in the management of osteoporosis remains largely unknown. To this end, ovariectomized (OVX) rats and primary osteoblasts were administrated with FLL aqueous extract and medicated serum, respectively. Supplement of FLL to OVX rats maintains bone quality by attenuating the reduction in bone mineral density, strength and microstructure. The maintenance may be associated with upregulating the expression of insulin-like growth factor-1, osteoprotegerin, phospho (p)-low-density lipoprotein receptor-related protein 6, p-glycogen synthase kinase 3 beta (GSK3β), β-catenin, Runx2 and c-Myc, and downregulating the expressions of sclerostin (SOST), dickkopf-related protein 1 (DKK1), GSK3β and p-β-catenin in rat femurs and tibias. In addition, the medicated serum promotes osteoblastic bone formation through activation of Wnt/β-catenin signaling via inhibition of DKK1 and SOST overexpression. Salidroside may be one of the active ingredients in FLL that are beneficial for bone homeostasis. In summary, our results suggest that FLL may preserve bone quality through induction of canonical Wnt/β-catenin signaling via inhibition of DKK1 and SOST overexpression. And FLL may offer a new source of the DKK1 or SOST inhibitors in protection against osteoporosis.

Keywords: Fructus Ligustri Lucidi; Wnt/β-catenin; bone quality; medicated serum; ovariectomized rats; primary osteoblasts.

MeSH terms

  • Alendronate
  • Animals
  • Bone Density / drug effects
  • Bone Morphogenetic Proteins / metabolism
  • Bone and Bones / drug effects*
  • Drugs, Chinese Herbal / therapeutic use
  • Female
  • Fruit / chemistry
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Ligustrum / chemistry*
  • Osteoblasts / drug effects
  • Osteoporosis / drug therapy*
  • Ovariectomy
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Wnt Signaling Pathway / drug effects*

Substances

  • Bone Morphogenetic Proteins
  • Dkk1 protein, rat
  • Drugs, Chinese Herbal
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Plant Extracts
  • Sost protein, rat
  • Alendronate