Abraham L A, Jenkins A L, Stone S R, Mackie E J
Department of Veterinary Basic Sciences, The Royal Veterinary College, London, United Kingdom.
J Bone Miner Res. 1998 May;13(5):818-27. doi: 10.1359/jbmr.1998.13.5.818.
Thrombin, a serine protease with a central role in thrombosis and hemostasis, is also a specific agonist for a variety of cellular responses in osteoblasts and stimulates bone resorption in organ culture. Cultured osteoblast-like cells express the proteolytically activated thrombin receptor, but the significance of this finding in vivo remains unknown. Immunohistochemistry was used to investigate the normal tissue distribution of the proteolytically activated thrombin receptor in developing rat bones and associated tissues. In hind limbs, the receptor was first observed on embryonic day 16 and became more abundant within the limb as gestation progressed. Thrombin receptor staining was detected on osteoblasts, macrophages, muscle cells, and endothelial cells, but not osteoclasts. Similarly, osteoblasts in developing calvariae stained positively for the thrombin receptor. The pattern of receptor expression by primary osteoblast cultures and freshly isolated macrophages and osteoclasts corresponded to that observed in vivo. The observed pattern of thrombin receptor expression in bone cells supports the hypothesis that cell-mediated thrombin-induced bone resorption is mediated by osteoblasts.
凝血酶是一种在血栓形成和止血过程中起核心作用的丝氨酸蛋白酶，它也是成骨细胞中多种细胞反应的特异性激动剂，并能刺激器官培养中的骨吸收。培养的成骨样细胞表达经蛋白水解激活的凝血酶受体，但这一发现在体内的意义仍不清楚。免疫组织化学被用于研究经蛋白水解激活的凝血酶受体在发育中的大鼠骨骼及相关组织中的正常组织分布。在后肢中，该受体最早在胚胎第16天被观察到，并且随着妊娠进展在肢体中变得更加丰富。在成骨细胞、巨噬细胞、肌肉细胞和内皮细胞上检测到凝血酶受体染色，但在破骨细胞上未检测到。同样，发育中的颅骨中的成骨细胞对凝血酶受体染色呈阳性。原代成骨细胞培养物以及新鲜分离的巨噬细胞和破骨细胞的受体表达模式与体内观察到的一致。在骨细胞中观察到的凝血酶受体表达模式支持这样一种假说，即细胞介导的凝血酶诱导的骨吸收是由成骨细胞介导的。
