Protective Role of β-Sitosterol in Glucocorticoid-Induced Osteoporosis in Rats Via the RANKL/OPG Pathway

Altern Ther Health Med. 2022 Oct;28(7):18-25.

Abstract

Introduction: Osteoporosis affects approximately 10% of the population worldwide. β-sitosterol (BSS), a major phytosterol in plants, has been claimed for centuries to have numerous medical benefits, including bone strengthening. This study aimed to find the benefit of BSS in treating osteoporosis according to traditional methods and to investigate the protective effect of BSS on glucocorticoid-induced osteoporosis in rats.

Design: Wistar rats were randomly assigned to one of four groups: the control group, the dexamethasone (DEX) group and one of two BSS-treated osteoporosis groups (100 and 200 mg/kg). Blood samples and femur bones were collected for histopathology, immunohistochemistry, biochemical and mRNA expression analysis.

Results: The results indicated that BSS (100 and 200 mg/kg) increased bone length, bone weight and bone mineral density (BMD) and suppressed DEX-induced reduction in body weight, dose-dependently. Mechanistically, BSS (100 and 200 mg/kg) treatment alleviated the increase of bone resorption markers and the decline of osteogenic markers, which might be partially mediated by regulation of nuclear factor kappa-β ligand/osteoprotegerin (RANKL/OPG) and RunX2 pathways. The immunohistochemical inducible nitric oxide synthase (iNOS) results of the rats' distal femur were negative in all groups. However, except in the DEX group, the endothelial nitric oxide synthase (eNOS) color reaction in osteoblasts was strongly positive in the other 3 groups. These results suggest that BSS showed promising effects in protection against glucocorticoid-induced osteoporosis by protecting osteoblasts and suppressing osteoclastogenesis.

MeSH terms

  • Animals
  • Bone Density
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Core Binding Factor Alpha 1 Subunit / pharmacology
  • Dexamethasone
  • Glucocorticoids
  • Ligands
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type II / pharmacology
  • Nitric Oxide Synthase Type III / metabolism
  • Nitric Oxide Synthase Type III / pharmacology
  • Osteoporosis* / chemically induced
  • Osteoporosis* / drug therapy
  • Osteoporosis* / prevention & control
  • Osteoprotegerin* / genetics
  • Osteoprotegerin* / metabolism
  • RANK Ligand / metabolism
  • RNA, Messenger / pharmacology
  • Rats
  • Rats, Wistar
  • Sitosterols

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Glucocorticoids
  • Ligands
  • Osteoprotegerin
  • RANK Ligand
  • RNA, Messenger
  • Sitosterols
  • Tnfrsf11b protein, rat
  • gamma-sitosterol
  • Dexamethasone
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III