Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bone. 2012 Jul;51(1):85-92. doi: 10.1016/j.bone.2012.04.006. Epub 2012 Apr 19.
Osteoprogeterin (OPG) plays an important role in regulating bone homeostasis by inhibiting osteoclastogenesis and bone resorption. Icariin is the major ingredient of Herba Epimedii, which exerts anabolic and anti-resorptive effects on bone, but the mechanism remains unknown. In this study, we evaluated the role of OPG in Icariin-mediated beneficial effects on bone.
Twelve-week-old Opg knockout (KO) male mice and their wild type (WT) littermates were orally administered with Icariin (0.3 mg/g) everyday for 8 weeks. Bone mass and microstructure in the right proximal tibiae were analyzed with micro-computed tomography (μCT). Bone remodeling was evaluated with serum biochemical analyses and bone histomorphometry. The colonies of fibroblast and osteoblast from bone marrow derived cells were quantified. The mRNA expressions of osteoblast and osteoclast related genes in trabecular bone from the femora were analyzed by real-time PCR.
Icariin treatment led to greater trabecular bone volume and trabecular number compared with vehicle treatment in WT mice. Icariin treatment increased bone formation parameters while it decreased bone resorption parameters in WT mice; however, the anabolic response of trabecular bone to Icariin treatment was diminished in KO mice. At cellular and molecular levels, Icariin significantly increased the formation of osteoblast colonies from bone marrow derived cells and the Opg gene expression in trabecular bone of WT mice.
These data suggest that Icariin treatment exerted anabolic and anti-resorptive effects on trabecular bone of WT mice, in which the effects were diminished in KO mice. The effects of Icariin treatment on bone are dependent on up-regulation of Opg, therefore, OPG plays an essential role in Icariin-mediated beneficial effects on trabecular bone.
护骨素（OPG）通过抑制破骨细胞生成和骨吸收，在调节骨稳态方面发挥重要作用。淫羊藿苷是淫羊藿的主要成分，对骨骼具有合成代谢和抗吸收作用，但作用机制尚不清楚。在这项研究中，我们评估了 OPG 在淫羊藿苷介导的骨有益作用中的作用。
12 周龄的 Opg 敲除（KO）雄性小鼠及其野生型（WT）同窝仔鼠每天口服给予淫羊藿苷（0.3mg/g），共 8 周。使用微计算机断层扫描（μCT）分析右侧胫骨近端的骨量和微结构。通过血清生化分析和骨组织形态计量学评估骨重塑。从骨髓来源细胞中量化成纤维细胞和破骨细胞的集落。通过实时 PCR 分析股骨小梁骨中与成骨细胞和破骨细胞相关的基因的 mRNA 表达。
与载体处理相比，淫羊藿苷处理导致 WT 小鼠的小梁骨体积和小梁数增加。淫羊藿苷处理增加了 WT 小鼠的骨形成参数，同时降低了骨吸收参数；然而，KO 小鼠的小梁骨对淫羊藿苷处理的合成代谢反应减弱。在细胞和分子水平上，淫羊藿苷显著增加了 WT 小鼠骨髓来源细胞中成骨细胞集落的形成和小梁骨中 Opg 基因的表达。
这些数据表明，淫羊藿苷处理对 WT 小鼠的小梁骨具有合成代谢和抗吸收作用，而在 KO 小鼠中作用减弱。淫羊藿苷处理对骨骼的作用依赖于 Opg 的上调，因此，OPG 在淫羊藿苷介导的小梁骨有益作用中发挥重要作用。
