Hausser Heinz-Juergen, Brenner Rolf E
University of Ulm, Division for Biochemistry of Joint and Connective Tissue Diseases, Ulm, Germany.
J Cell Biochem. 2004 Apr 1;91(5):1062-73. doi: 10.1002/jcb.20007.
Long-term treatment with heparin has been associated with an increased risk of osteoporosis. Given the importance of heparan sulfate proteoglycans for bone metabolism, it can be anticipated that heparin due to its structural similarity with heparan sulfate chains somehow interferes with the biological activities of these cell surface- and extracellular matrix-associated molecules. Initially in order to study the effect(s) of heparin on osteoblasts that possibly contribute to the development of heparin-induced osteoporosis, we treated osteoblast-like Saos-2 cells in monolayer culture for different periods of time with different concentrations of heparin. None of the heparin concentrations tested led to an inhibition of osteoblast proliferation during the early proliferative phase. After longer incubation times, however, cultures treated with higher concentrations of heparin (>/=5 microg/ml) exhibited a reduction in cell number as well as an inhibition of matrix deposition and mineralization. These effects could not be observed with lower heparin concentrations. On the contrary, low concentrations of heparin (5-500 ng/ml) even promoted matrix deposition and its subsequent mineralization. Apparently, heparin has a biphasic effect on osteoblast-like Saos-2 cells, being inhibitory at high concentrations but stimulatory at low concentrations. These results imply that heparin at concentrations well below those used for antithrombotic therapy might eventually turn out to be beneficial for bone formation.
长期使用肝素与骨质疏松症风险增加有关。鉴于硫酸乙酰肝素蛋白聚糖对骨代谢的重要性，可以预期，由于肝素与硫酸乙酰肝素链结构相似，它会以某种方式干扰这些与细胞表面和细胞外基质相关分子的生物学活性。最初，为了研究肝素对可能导致肝素诱导的骨质疏松症的成骨细胞的影响，我们在单层培养中用不同浓度的肝素对成骨样Saos-2细胞进行了不同时间段的处理。在早期增殖阶段，所测试的肝素浓度均未导致成骨细胞增殖受到抑制。然而，经过更长的孵育时间后，用较高浓度肝素（≥5微克/毫升）处理的培养物显示细胞数量减少以及基质沉积和矿化受到抑制。较低的肝素浓度未观察到这些作用。相反，低浓度肝素（5 - 500纳克/毫升）甚至促进了基质沉积及其随后的矿化。显然，肝素对成骨样Saos-2细胞具有双相作用，高浓度时具有抑制作用，而低浓度时具有刺激作用。这些结果表明，浓度远低于抗血栓治疗所用浓度的肝素最终可能对骨形成有益。
