Effects of yuja peel extract and its flavanones on osteopenia in ovariectomized rats and osteoblast differentiation

Mol Nutr Food Res. 2016 Dec;60(12):2587-2601. doi: 10.1002/mnfr.201600257. Epub 2016 Sep 20.

Abstract

Scope: Yuja (Citrus junos Tanaka) possesses various health benefits, but its effects on bone health are unknown. In this study, the preventative effects of yuja peel ethanol extract (YPEE) on osteopenia were determined in ovariectomized (OVX) rats, and the mechanisms by which YPEE and its flavanones regulate osteoblastogenesis were examined in vitro.

Methods and results: The effects of YPEE on osteoblastogenesis were investigated in MC3T3-E1 cells. YPEE promoted alkaline phosphatase (ALP) activity, mineralization, and the expression of osteoblast differentiation marker genes, such as ALP, runt-related transcription factor 2 (Runx2), and osteocalcin. YPEE and its flavanones promoted osteoblast differentiation via BMP-2-mediated p38 and the Smad1/5/8 signaling pathway. YPEE supplementation significantly decreased body weight and increased uterine weight and bone mineral density in OVX rats. Based on a micro-CT analysis of femurs, YPEE significantly attenuated osteopenia and increased trabecular volume fraction, trabecular separation, and trabecular number (p < 0.05).

Conclusion: Dietary YPEE has a protective effect on OVX-induced osteopenia. YPEE and its flavanones promote osteoblastogenesis via the activation of the BMP/p38/Smad/Runx2 pathways. These results extend our knowledge of the beneficial effects of YPEE and provide a basis for the development of novel therapies for osteoporosis.

Keywords: Flavanones; Osteoblastogenesis; Osteopenia; Ovariectomized; Yuja (Citrus junos Tanaka).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Density / drug effects
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism
  • Cell Differentiation / drug effects*
  • Citrus / chemistry
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Dyslipidemias / drug therapy
  • Dyslipidemias / etiology
  • Female
  • Flavanones / pharmacology*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis / drug effects*
  • Ovariectomy
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Smad Proteins, Receptor-Regulated / genetics
  • Smad Proteins, Receptor-Regulated / metabolism

Substances

  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Flavanones
  • Plant Extracts
  • Runx2 protein, rat
  • Smad Proteins, Receptor-Regulated
  • Osteocalcin
  • Alkaline Phosphatase