Cbfa-1 (Runx-2) and Osteocalcin Expression by Human Osteoblasts in Heparin Osteoporosis in Vitro

Handschin, Alexander E. MD
Egermann, Marcus MD
Trentz, Otmar MD
Wanner, Guido A. MD
Kock, Hans-Jürgen MD
Zünd, Gregor MD
Trentz, Omana Anna MD

^*Department of Surgery, Research Division, University Hospital of Zurich, Switzerland
^†Division of Trauma Surgery, University Hospital of Zurich, Switzerland
^‡Division of Trauma Surgery, Hochtaunus Kliniken, Bad Homburg, Germany

Address correspondence to Alexander E. Handschin, MD, Department of Surgery, Research Division, University Hospital of Zurich, Switzerland; e-mail: [email protected].

Clinical & Applied Thrombosis/Hemostasis 12(4):p 465-472, October 2006.

Summary

Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.