Iguratimod prevents ovariectomy‑induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator‑activated receptor‑γ.
Iguratimod prevents ovariectomy‑induced bone loss and suppresses osteoclastogenesis via inhibition of peroxisome proliferator‑activated receptor‑γ.
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iguratimod可防止卵巢切除术引起的骨质流失，并通过抑制过氧化物酶体增殖物激活的受体−γ抑制破骨细胞的发生。
DOI：
10.3892/mmr.2017.7648
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
Guo FJ
中科院分区：
文献类型：
--
作者：
Wu YX;Sun Y;Ye YP;Zhang P;Guo JC;Huang JM;Jing XZ;Xiang W;Yu SY;Guo FJ
艾拉莫德因其抗炎活性和对类风湿性关节炎患者的治疗作用而闻名。先前已经证明，在步行者256大鼠乳腺癌细胞诱导的骨癌疼痛模型中，iguratimod减弱骨破坏和破骨细胞形成。因此，假设iguratimod可能另外对良性破骨细胞相关疾病（包括绝经后骨质疏松症）表现出治疗作用。在本研究中，使用卵巢切除小鼠来研究iguratimod在体内的作用。体外培养骨髓单个核细胞，观察艾拉莫德对核因子-κB受体激活因子配体（RANKL）诱导的破骨细胞生成的影响及其分子机制。已经证明，iguratimod可以通过抑制体内破骨细胞活性来预防卵巢切除术诱导的骨丢失。因此，iguratimod可以抑制RANKL诱导的破骨细胞生成和原代骨髓单个核细胞的骨吸收。在分子水平上，iguratimod抑制了过氧化物酶体增殖物激活受体-γ（PPAR-γ）/c-Fos通路，该通路在RANKL诱导的破骨细胞分化中至关重要。随后，iguratimod降低活化T细胞核因子c1和下游破骨细胞标志物基因的表达。本研究的结果表明，iguratimod可以通过调节RANKL信号传导抑制卵巢切除术诱导的骨丢失和破骨细胞生成。因此，iguratimod可能作为一种新的治疗，以预防绝经后骨质疏松症。
Iguratimod is known for its anti-inflammatory activities and therapeutic effects in patients with rheumatoid arthritis. It has previously been demonstrated that iguratimod attenuates bone destruction and osteoclast formation in the Walker 256 rat mammary gland carcinoma cell-induced bone cancer pain model. Therefore, it was hypothesized that iguratimod may additionally exhibit therapeutic effects on benign osteoclast-associated diseases including postmenopausal osteoporosis. In the present study, ovariectomized mice were used to investigate the effects of iguratimod in vivo. Bone marrow mononuclear cells were cultured to detect the effects of iguratimod on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and the molecular mechanisms involved. It was demonstrated that iguratimod may prevent ovariectomy-induced bone loss by suppressing osteoclast activity in vivo. Consistently, iguratimod may inhibit RANKL-induced osteoclastogenesis and bone resorption in primary bone marrow mononuclear cells. At the molecular level, peroxisome proliferator-activated receptor-γ (PPAR-γ)/c-Fos pathway, which is essential in RANKL-induced osteoclast differentiation, was suppressed by iguratimod. Subsequently, iguratimod decreased the expression of nuclear factor of activated T cells c1 and downstream osteoclast marker genes. The results of the present study demonstrated that iguratimod may inhibit ovariectomy-induced bone loss and osteoclastogenesis by modulating RANKL signaling. Therefore, iguratimod may act as a novel therapeutic to prevent postmenopausal osteoporosis.
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影响因子：
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