Dept. of Biological Sciences (BK21 Program) and the Immunomodulation Research Center, Univ. of Ulsan, Ulsan, Korea.
Am J Physiol Endocrinol Metab. 2012 Dec 1;303(11):E1296-303. doi: 10.1152/ajpendo.00085.2012. Epub 2012 Sep 4.
The aim of the present study was to evaluate the effect of fibrinogen on number and function of osteoclasts (OC) consequently resulting in bone loss. It was hypothesized that the enhanced level of released fibrinogen due to loss of ovarian function caused bone loss by acting on OCs. Bone loss was induced by ovariectomy (OVX) in mice and analyzed by micro-CT. The effect of fibrinogen on OCs was evaluated by tartrate-resistant acid phosphatase, annexin V, actin staining, pit formation observed on dentine slices, and Western blotting. Exogenous fibrinogen increased OC survival, actin ring formation, and bone resorption in vitro. The effect of fibrinogen was dependent on β(3)-integrin, which is a marker for mature OCs. Fibrinogen induced the activation of transforming oncogene from Ak strain (Akt), Ras-related C3 botulinum toxin substrate 1 (Rac1), and Rho family of GTPase (Rho) and the degradation of the Bcl-2 interacting mediator of cell death (Bim) in a manner similar to macrophage colony-stimulating factor (M-CSF). OVX increased plasma fibrinogen and serum M-CSF together with elevated actin ring formation and bone loss. The increased fibrinogen level due to loss of ovarian function may contribute, at least partly, to bone loss through the enhanced number and activity of OCs.
本研究旨在评估纤维蛋白原对破骨细胞（OC）数量和功能的影响，从而导致骨质流失。研究假设由于卵巢功能丧失而释放的纤维蛋白原水平升高，通过作用于 OC 导致骨质流失。通过卵巢切除术（OVX）在小鼠中诱导骨质流失，并通过 micro-CT 进行分析。通过抗酒石酸酸性磷酸酶、膜联蛋白 V、肌动蛋白染色、牙本质切片上观察到的陷窝形成以及 Western blot 评估纤维蛋白原对 OC 的作用。纤维蛋白原体外增加 OC 的存活、肌动蛋白环形成和骨吸收。纤维蛋白原的作用依赖于 β(3)-整合素，β(3)-整合素是成熟 OC 的标志物。纤维蛋白原诱导 AK 株转化癌基因（Akt）、Ras 相关 C3 肉毒杆菌毒素底物 1（Rac1）和 Rho 家族 GTP 酶（Rho）的激活，并以类似于巨噬细胞集落刺激因子（M-CSF）的方式降解 Bcl-2 相互作用的细胞死亡介体（Bim）。OVX 增加血浆纤维蛋白原和血清 M-CSF，同时增加肌动蛋白环形成和骨质流失。由于卵巢功能丧失而增加的纤维蛋白原水平可能通过增加 OC 的数量和活性来促进骨质流失。
