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Clinical and Applied Thrombosis/Hemostasis, Vol. 12, No. 4, 465-472 (2006)
DOI: 10.1177/1076029606293433

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

Alexander E. Handschin, MD

Department of Surgery, Research Division, University Hospital of Zurich, Switzerland, alexander.handschin{at}usz.ch

Marcus Egermann, MD

Department of Surgery, Research Division, University Hospital of Zurich, Switzerland

Otmar Trentz, MD

Division of Trauma Surgery, University Hospital of Zurich, Switzerland

Guido A. Wanner, MD

Division of Trauma Surgery, University Hospital of Zurich, Switzerland

Hans-Jürgen Kock, MD

Division of Trauma Surgery, Hochtaunus Kliniken, Bad Homburg, Germany

Gregor Zünd, MD

Department of Surgery, Research Division, University Hospital of Zurich, Switzerland

Omana Anna Trentz, MD

Department of Surgery, Research Division, University Hospital of Zurich, Switzerland

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.

Key Words: Heparin osteoporosis • Osteoblast • Osteocalcin • Cbfa-1


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