Expression of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in rat osteoporosis induced by immunosuppressant FK506
Expression of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in rat osteoporosis induced by immunosuppressant FK506
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DOI：
10.1016/j.bone.2003.05.003
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发表时间：
2004-03-01
期刊：
影响因子：
4.1
通讯作者：
Sugahara, T
中科院分区：
文献类型：
--
作者：
Fukunaga, J;Yamaai, T;Sugahara, T
免疫抑制剂药物目前需要移植受者的余生，尽管与这些治疗相关的许多不良反应。急性骨质疏松症就是这样一种效应，并且已经通过在大鼠中施用免疫抑制剂药物FK 506建立了可再现的骨质疏松症模型。这种骨质疏松症的原因已被证明是破骨细胞异常增殖。改变骨骼重塑的过程然而，FK 506诱导破骨细胞增殖的原因以及该过程是否由细胞因子变化或骨吸收因子的增加介导尚不清楚，因此，针对最近发现的破骨细胞分化因子（ODF）和破骨细胞生成抑制因子（OCIF）进行了调查。这些因素导致破骨细胞分化成熟机制的阐明。采用连续28天肌肉注射FK 506（1 mg/kg）的方法在大鼠中建立骨质疏松症模型。在FK 506组中观察到小梁骨吸收劣于软骨内骨化，并且抗酒石酸酸性磷酸酶（TRAP）染色显示，相对于对照组，软骨内骨化部位的破骨细胞明显增加。实时PCR和原位杂交（ISH）显示对照组和治疗组之间OCIF表达的差异极小。然而，实时PCR显示治疗组中ODF表达明显增加。在使用ISH的治疗组中，ODF表达也显示出增加。这在组织学上与破骨细胞增殖低于内软骨骨化的区域一致。本研究结果支持以下假设：FK 506介导的骨质疏松症是通过药物对破骨细胞的作用，促进ODF信使核糖核酸（mRNA）的表达，从而促进破骨细胞分化和成熟而发生的。(C)2003年爱思唯尔公司All rights reserved.
Immunosuppressant drugs are currently required by transplant recipients for the remainder of their lives, despite the many adverse effects associated with these therapies. Acute osteoporosis is one such effect, and a reproducible osteoporosis model has been established through the administration of the immunosuppressant drug FK506 in rats. The cause of this osteoporosis has been shown to be abnormal osteoclast proliferation.. altering the process of bone remodeling. However, the reasons why FK506 induces osteoclast proliferation and whether this process is mediated by cytokine changes or an increase in bone resorption factors have been unclear, An investigation was therefore conducted focusing on the recent discoveries of osteoclast differentiation factor (ODF) and osteoclastogenesis inhibitory factor (OCIF). These factors led to elucidation of the osteoclast differentiation-maturation mechanism. An osteoporosis model was produced in rats utilizing intramuscular FK506 injection (1 mg/kg) for 28 consecutive days. Trabecular bone resorption was observed inferior to enchondral ossification in the FK506 group, and tartrate resistant acid phosphatase (TRAP) staining revealed a clear increase in osteoclasts at the site of enchondral ossification, relative to the control group. Real-time PCR and in situ hybridization (ISH) demonstrated minimal differences in OCIF expression between control and the treatment groups. However, Real-time PCR revealed clearly increased ODF expression in the treatment group. ODF expression was also shown to be increased in the treatment group using ISH. This was histologically consistent with a region of osteoclast proliferation inferior to enchondral ossification. The results of this study support the hypothesis that FK506-mediated osteoporosis occurs by action of the drug on osteoclasts, promoting expression of ODF messenger ribonucleic acid (mRNA) and thus prompting osteoclast differentiation and maturation. (C) 2003 Elsevier Inc. All rights reserved.