Rozen N, Ish-Shalom S, Rachmiel A, Stein H, Lewinson D
Department of Orthopedic Surgery A, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Bone. 2000 May;26(5):469-74. doi: 10.1016/S8756-3282(00)00263-5.
A great deal of evidence has been accumulating that implicates the immune system in normal and pathological bone turnover. The objective of the present study was to examine the possible involvement of cytokines produced by T lymphocytes in bone metabolism. We have chosen the immunologically compromised athymic mouse, which demonstrate sclerotic features in its trabecular bone, as the animal model for assessment of possible modulation effects of interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6) on bone and cartilage metabolism. The cytokines were applied by daily subcutaneous injections for 3 consecutive days. Histomorphometry, measuring epiphyseal trabecular bone volume (ETBV), metaphyseal trabecular bone volume (MTBV), and the width of the growth plate, and tartrate-resistant acid phosphatase (TRAP) histochemistry were used to assess parameters of bone turnover in the proximal tibia. IL-6, but not IL-1alpha, reduced ETBV and MTBV. Both IL-6 and IL-1alpha reduced the width of the growth plate. IL-6, but not IL-1alpha, increased the number of chondroclasts and osteoclasts in the primary spongiosa of the proximal tibia, as well as the number of nuclei. The resultant bone resembled that of the wild-type mouse. The results point to IL-6 as a possible regulator of bone turnover in vivo. It is suggested that the athymic mouse has a deficiency somewhere in the cascade of events leading to the production of IL-6 or, alternatively, that IL-6 replaces other factors that are supplied by T lymphocytes directly or indirectly. As T lymphocytes interact with B lymphocytes it is suggested that the athymic mouse might be appropriate for studying the in vivo effects of the immune system on normal bone metabolism.
越来越多的证据表明，免疫系统参与正常和病理性的骨转换。本研究的目的是检测T淋巴细胞产生的细胞因子在骨代谢中可能发挥的作用。我们选择免疫功能受损的无胸腺小鼠作为动物模型，评估白细胞介素-1α（IL-1α）和白细胞介素-6（IL-6）对骨和软骨代谢的可能调节作用，该小鼠的小梁骨呈现硬化特征。通过连续3天每日皮下注射给予细胞因子。采用组织形态计量学方法测量骨骺小梁骨体积（ETBV）、干骺端小梁骨体积（MTBV）和生长板宽度，并运用抗酒石酸酸性磷酸酶（TRAP）组织化学方法评估胫骨近端的骨转换参数。IL-6而非IL-1α降低了ETBV和MTBV。IL-6和IL-1α均减小了生长板宽度。IL-6而非IL-1α增加了胫骨近端初级海绵体中破软骨细胞和破骨细胞的数量以及细胞核数量。所形成的骨与野生型小鼠的骨相似。结果表明IL-6可能是体内骨转换的调节因子。提示无胸腺小鼠在导致IL-6产生的一系列事件中的某个环节存在缺陷，或者IL-6替代了由T淋巴细胞直接或间接提供的其他因子。由于T淋巴细胞与B淋巴细胞相互作用，因此提示无胸腺小鼠可能适合用于研究免疫系统对正常骨代谢的体内作用。
