The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae
The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae
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肿瘤坏死因子2型受体在肿瘤坏死因子α诱导的小鼠颅骨骨吸收陷窝中发挥保护作用
DOI：
10.1007/s00774-011-0270-z
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
K.Aoki
中科院分区：
文献类型：
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作者：
K.Nagano;N.Alles;A.H.Mian;A.Shimoda;N.Morimoto;Y.Tamura;H.Shimokawa;K.Akiyoshi;K.Ohya;K.Aoki
肿瘤坏死因子（TNF）-α通过TNF 1型和2型受体（TNFR 1和TNFR 2）发挥其生物学功能。我们以前曾报道过，TNFR 2缺陷小鼠中脂多糖（LPS）诱导的骨吸收比野生型（WT）小鼠加速。虽然这些结果表明TNFR 2可能在骨吸收中具有保护作用，但我们不能排除TNFR 2在骨吸收中没有作用的可能性。为了阐明TNFR 2的作用，我们开发了一种TNF-α诱导的骨吸收模型，使用含胆固醇的普鲁兰多糖纳米凝胶作为TNF-α载体，以最大限度地减少TNF-α以外的炎性细胞因子的影响。注射人TNF-α（hTNF）（小鼠TNFR 1的激动剂）可刺激WT小鼠颅骨上的骨吸收陷窝，但小鼠TNF-α（mTNF）（小鼠TNFR 1和TNFR 2的激动剂）则不能。为了排除hTNF的TNFR 1激动作用强于mTNF的可能性，我们在TNFR 2缺陷小鼠中使用了相同的模型。注射mTNF导致明显的骨吸收陷窝，与在TNFR 2缺陷小鼠中使用hTNF后观察到的程度相同。破骨细胞数量的组织形态计量学分析支持骨吸收陷窝的变化。这些数据表明TNFR 2在TNF-α诱导的骨吸收中具有保护作用。
Tumor necrosis factor (TNF)-α exerts its biological function via TNF type 1 and type 2 receptors (TNFR1 and TNFR2). We have previously reported that bone resorption induced by lipopolysaccharide (LPS) in TNFR2-deficient mice is accelerated compared to that in wild-type (WT) mice. Although these results suggested that TNFR2 might have a protective role in bone resorption, we could not exclude the possibility that TNFR2 has no role in bone resorption. To clarify the role of TNFR2, we developed a TNF-α-induced bone resorption model using cholesterol-bearing pullulan nanogel as a TNF-α carrier to minimize the influence of inflammatory cytokines other than TNF-α. Injections of human TNF-α (hTNF), an agonist of mouse TNFR1, stimulated bone resorption lacunae on the calvariae in WT mice, but mouse TNF-α (mTNF), an agonist of both mouse TNFR1 and TNFR2, could not. To eliminate the possibility that the TNFR1 agonistic effects of hTNF were stronger than those of mTNF, we used the same model in TNFR2-deficient mice. Injection of mTNF resulted in clear bone resorption lacunae to the same extent observed after using hTNF in the TNFR2-deficient mice. Histomorphometric analysis of osteoclast number supported the observed changes in bone resorption lacunae. These data suggest that TNFR2 has a protective role in TNF-α-induced bone resorption.