Journal of Bone and Mineral Metabolism

, Volume 28, Issue 3, pp 276–288

Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation

Authors

  • Ignazio Barbagallo
    • Department of Biological Chemistry, Medical Chemistry and Molecular BiologyUniversity of Catania
  • Angelo Vanella
    • Department of Biological Chemistry, Medical Chemistry and Molecular BiologyUniversity of Catania
  • Stephen J. Peterson
    • Department of MedicineNew York Medical College
  • Dong Hyun Kim
    • Department of Physiology and PharmacologyUniversity of Toledo College of Medicine
  • Daniele Tibullo
    • Department of Biomedical Sciences, Section of HematologyUniversity of Catania
  • Cesarina Giallongo
    • Department of Biomedical Sciences, Section of HematologyUniversity of Catania
  • Luca Vanella
    • Department of Physiology and PharmacologyUniversity of Toledo College of Medicine
  • Nunziatina Parrinello
    • Department of Biomedical Sciences, Section of HematologyUniversity of Catania
  • Giuseppe A. Palumbo
    • Department of Biomedical Sciences, Section of HematologyUniversity of Catania
  • Francesco Di Raimondo
    • Department of Biomedical Sciences, Section of HematologyUniversity of Catania
    • Department of Physiology and PharmacologyUniversity of Toledo College of Medicine
    • Department of MedicineNew York Medical College
  • David Asprinio
    • Department of OrthopedicsNew York Medical College
Original Article

DOI: 10.1007/s00774-009-0134-y

Cite this article as:
Barbagallo, I., Vanella, A., Peterson, S.J. et al. J Bone Miner Metab (2010) 28: 276. doi:10.1007/s00774-009-0134-y

Abstract

Human bone marrow mesenchymal stem cells (MSCs) are pleiotrophic cells that differentiate to either adipocytes or osteoblasts as a result of crosstalk by specific signaling pathways including heme oxygenase (HO)-1/-2 expression. We examined the effect of inducers of HO-1 expression and inhibitors of HO activity on MSC differentiation to the osteoblast and following high glucose exposure. MSC cultured in osteogenic medium increased expression of osteonectin, Runt-related transcription factor 2 (RUNX-2), osteocalcin, and alkaline phosphatase. HO-1 expression during differentiation was initially decreased and then followed by a rebound increase after 15 days of culture. Additionally, the effect of HO-1 on osteoblasts appears different to that seen in adipocyte stem cells. On addition of a cobalt compound, the resultant induction of HO-1 decreases adipogenesis. Moreover, glucose (30 mM) inhibited osteoblast differentiation, as evidenced by decreased bone morphogenetic protein (BMP)-2, osteonectin, osteocalcin, and osteoprotegerin (OPG). In contrast, MSC-derived adipocytes were increased by glucose. Increased HO-1 expression increased the levels of osteonectin, OPG, and BMP-2. Inhibition of HO activity prevented the increase in osteonectin and potentiated the decrease of osteocalcin and OPG in cells exposed to high glucose levels. Furthermore, targeting HO-1 expression increased pAMPK and endothelial nitric oxide synthase (eNOS) and restored osteoblastic markers. Our findings suggest that targeting HO-1 gene expression attenuates the hyperglycemia-mediated decrease in MSC-derived osteoblast differentiation. Finally, the mechanism underlying the HO-1-specific cell effect on osteoblasts and adipocytes is yet to be explored. Thus, the targeting of HO-1 gene expression presents a portal to increase osteoblast function and differentiation and attenuate osteoporosis by promoting bone formation.

Keywords

Osteopenia Osteoporosis MSC Diabetes HO-1

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2009