Handschin Alexander E, Egermann Marcus, Trentz Otmar, Wanner Guido A, Kock Hans-Jürgen, Zünd Gregor, Trentz Omana Anna
Department of Surgery, Research Division, University Hospital of Zurich, Switzerland.
Clin Appl Thromb Hemost. 2006 Oct;12(4):465-72. doi: 10.1177/1076029606293433.
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.
长期应用肝素可能会对骨形成产生不良反应。确切的发病机制尚不清楚,但体外数据表明成骨细胞功能受损。Cbfa-1(Runx-2)和骨钙素的转录轴对于维持体内骨形成和吸收的平衡至关重要。我们使用人成骨细胞培养模型进一步研究肝素(低分子量肝素,达肝素)对这两种成骨细胞分化调节因子表达的影响。在高剂量时,达肝素在体外可显著抑制骨钙素和Cbfa-1的表达。我们的数据支持肝素诱导骨质疏松症背后存在成骨细胞功能直接抑制的假说。