Sass D A, Liss T, Bowman A R, Rucinski B, Popoff S N, Pan Z, Ma Y F, Epstein S
Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA.
J Bone Miner Res. 1997 Mar;12(3):479-86. doi: 10.1359/jbmr.1997.12.3.479.
Our laboratory has previously demonstrated that the T-lymphocyte is critical in the development of cyclosporin A-induced osteopenia in the rat model. A similar state of osteopenia is induced by estrogen depletion in the ovariectomized (OVX) rat, which is the animal model of postmenopausal bone loss. However, the role of the immune system, and particularly the T-lymphocyte, in estrogen deplete osteopenia has not been elucidated. We used the Rowett athymic nude rat as our model of T-lymphocyte deficiency. In this study, the experimental rats were divided into four groups as follows: (1) sham-operated Rowett heterozygous (rnu/+) euthymic rats (control group); (2) OVX Rowett heterozygous (rnu/+) euthymic rats; (3) sham-operated Rowett homozygous (rnu/rnu) athymic nude rats, which are T-lymphocyte deficient; and (4) ovariectomized Rowett homozygous (rnu/rnu) rats. Rats were weighed, and venous blood was taken in weeks 2, 4, and 6 for determination of serum osteocalcin. Serum 1,25-dihydroxyvitamin D (1,25(OH)2D) was determined on the day of sacrifice. Following sacrifice, histomorphometry was performed on double-labeled proximal tibial metaphyses. Flow cytometric analysis of splenic mononu-clear cell isolates stained for OX19-positive (CD5) T-lymphocytes was performed. T-lymphocyte analysis revealed significant reductions in both athymic nude groups, while OVX euthymic rats demonstrated a diminished number of T-cells relative to their sham-operated counterparts. Histomorphometric data indicated that both OVX groups exhibited a significant loss of trabecular volume, with associated increases in indices for bone formation and resorption, with resorption likely outstripping formation, resulting in osteopenia. Serum osteocalcin was significantly elevated in the ovariectomized euthymic group throughout the experimental period compared with the control group (p < 0.01); it was elevated in the ovariectomized athymic group on week 4 only (p < 0.01 vs. control). It appears that the T-lymphocyte may not be an essential component in the pathogenesis of estrogen deficiency osteopenia. The contribution of circulating T-lymphocytes as well as other T-lymphocyte-rich organs needs to be explored further.
我们实验室先前已证明，在大鼠模型中，T淋巴细胞在环孢素A诱导的骨质减少发展过程中起关键作用。去卵巢（OVX）大鼠因雌激素缺乏会引发类似的骨质减少状态，这是绝经后骨质流失的动物模型。然而，免疫系统，尤其是T淋巴细胞，在雌激素缺乏性骨质减少中的作用尚未阐明。我们使用罗威特无胸腺裸鼠作为T淋巴细胞缺乏的模型。在本研究中，实验大鼠分为以下四组：（1）假手术的罗威特杂合（rnu/+）有胸腺大鼠（对照组）；（2）去卵巢的罗威特杂合（rnu/+）有胸腺大鼠；（3）假手术的罗威特纯合（rnu/rnu）无胸腺裸鼠，其缺乏T淋巴细胞；（4）去卵巢的罗威特纯合（rnu/rnu）大鼠。对大鼠进行称重，并在第2、4和6周采集静脉血以测定血清骨钙素。在处死当天测定血清1,25 - 二羟基维生素D（1,25(OH)2D）。处死后，对胫骨近端干骺端进行双标记组织形态计量学分析。对脾脏单核细胞分离物进行流式细胞术分析，检测OX19阳性（CD5）T淋巴细胞。T淋巴细胞分析显示，两个无胸腺裸鼠组的T淋巴细胞数量均显著减少，而去卵巢有胸腺大鼠相对于假手术对照组的T细胞数量减少。组织形态计量学数据表明，两个去卵巢组的骨小梁体积均显著减少，同时骨形成和吸收指标增加，吸收可能超过形成，导致骨质减少。与对照组相比，去卵巢有胸腺组在整个实验期间血清骨钙素显著升高（p < 0.01）；去卵巢无胸腺组仅在第4周血清骨钙素升高（与对照组相比p < 0.01）。看来T淋巴细胞可能不是雌激素缺乏性骨质减少发病机制中的必要成分。循环T淋巴细胞以及其他富含T淋巴细胞的器官的作用有待进一步探索。
