Osteoporosis International

, Volume 22, Issue 2, pp 675–684

Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: the effect on differentiation in stem cells derived from bone marrow

  • R. Santiago-Mora
  • A. Casado-Díaz
  • M. D. De Castro
  • J. M. Quesada-Gómez
Original Article

DOI: 10.1007/s00198-010-1270-x

Cite this article as:
Santiago-Mora, R., Casado-Díaz, A., De Castro, M.D. et al. Osteoporos Int (2011) 22: 675. doi:10.1007/s00198-010-1270-x



The effects of oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells (MSCs) from human bone marrow have been studied. We report that oleuropein, a polyphenol abundant in olive tree products, reduces the expression of peroxisome proliferator-activated receptor gamma (PPARγ), inhibits adipocyte differentiation, and enhances differentiation into osteoblast.


Age-related bone loss is associated with osteoblast insufficiency during continuous bone remodeling. It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and age-related changes in this relationship could be responsible for the progressive adiposity of bone marrow which occurs with osteoporosis. In addition, the consumption of oleuropein, a major polyphenol in olive leaves and olive oil, has been associated with a reduction in bone loss.


We have analyzed the effects of oleuropein—at concentrations between 10−6 and 10−4 M—on the processes of osteoblastogenesis and adipogenesis in MSCs from human bone marrow.


The results show an increase in osteoblast differentiation and a decrease in adipocyte differentiation when there is oleuropein in the culture media. The gene expression of osteoblastogenesis markers, RUNXII, osterix, collagen type I, osteocalcin, or alkaline phosphatase (ALP), was higher in osteoblast-induced oleuropein-treated cells. Also, the ALP activity and extracellular matrix mineralization were higher when oleuropein was present in the media. Oleuropein in MSCs induced adipocytes to produce a decrease in the expression of the genes involved in adipogenesis, the PPARγ, lipoprotein lipase, or fatty acid-binding protein 4, and minor fat accumulation.


Our data suggest that oleuropein, highly abundant in olive tree products included in the traditional Mediterranean diet, could prevent age-related bone loss and osteoporosis.


AdipogenesisBone marrowMesenchymal stem cellOleuropeinOsteoblastogenesis

Supplementary material

198_2010_1270_Fig6_ESM.gif (15 kb)
Fig. S1

The oleuropein toxicity on MSC-h have been analyzed with an apoptosis test. There are no significant differences between the control (oleuropein untreated cells) and the culture treated with oleuropein. ***p < 0.001 vs untreated MSCs (GIF 14 kb)

198_2010_1270_MOESM1_ESM.tif (654 kb)
High-resolution image (TIFF 654 kb)
198_2010_1270_Fig7_ESM.gif (35 kb)
Fig. S2

Elocution crystal violet: the cellular density does not show difference when the oleuropein is or is not in the media (GIF 35 kb)

198_2010_1270_MOESM2_ESM.tif (980 kb)
High-resolution image (TIFF 979 kb)

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • R. Santiago-Mora
    • 1
    • 4
  • A. Casado-Díaz
    • 1
    • 2
    • 4
  • M. D. De Castro
    • 3
  • J. M. Quesada-Gómez
    • 1
    • 2
    • 4
  1. 1.Unidad Metabolismo MineralHospital Universitario Reina SofíaCórdobaSpain
  2. 2.SANYRES XXICórdobaSpain
  3. 3.Departamento de Química AnalíticaUniversidad de CórdobaCórdobaSpain
  4. 4.Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)CórdobaSpain