The influence of zoledronate and teriparatide on gamma delta T cells in mice
The influence of zoledronate and teriparatide on gamma delta T cells in mice
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唑来膦酸和特立帕肽对小鼠γδT细胞的影响
DOI：
10.1016/j.jds.2017.03.007
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Iida Seiji
中科院分区：
文献类型：
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作者：
Yamachika Eiki;Matsui Yuichi;Matsubara Masakazu;Matsumura Tatsushi;Nakata Naoki;Moritani Norifumi;Ikeda Atsushi;Tsujigiwa Hidetsugu;Ohara Naoya;Iida Seiji
背景/目的很少有研究调查了双膦酸盐相关性颌骨骨坏死（BRONJ）可能反映免疫反应的可能性；然而，研究显示，BRONJ患者血液中的γ δ T细胞显著下降。此外，有一些报道使用特立帕肽治疗BRONJ。在这项研究中，我们比较了唑来膦酸钠和特立帕肽对小鼠淋巴细胞群和炎症细胞因子产生的影响。材料与方法30只雌性ICR小鼠分为三组（每组10只）：载药组、唑来膦酸钠组和特立帕肽组。每组给药8周。血液和胸腺淋巴细胞分析，股骨进行组织学观察和骨髓淋巴细胞分析。使用Milliplex®多重免疫分析法测定分离血清中的细胞因子。结果唑来膦酸钠能降低小鼠骨髓T细胞数量。此外，在唑来膦酸钠处理的小鼠中，血清白细胞介素(IL)-2、IL-7、IL-12、IL-15和RANTES（影响T细胞活化、分化和/或增殖的细胞因子）水平显著降低。相反，特立帕肽治疗诱导外周血γ δ T细胞增加。结论唑来膦酸钠治疗可使骨髓γ δ T细胞减少，特立帕肽治疗可使骨髓γ δ T细胞增加。如果BRONJ涉及循环或骨髓中γ δ T细胞的损失，那么由特立帕肽诱导的γ δ T细胞的增加可能解释了其解决BRONJ的能力。
Background/purposeFew studies have investigated the possibility that bisphosphonate-related osteonecrosis of the jaw (BRONJ) might reflect an immune response; however, gamma delta T cells have been shown to significantly decline in the blood of BRONJ patients. Additionally, there have been some reports of teriparatide usage for the treatment of BRONJ. In this study, we compared the effects of zoledronate and teriparatide on lymphocyte populations and inflammatory cytokine production in mice.Materials and methodsThirty female ICR mice were divided into three groups (n = 10 each): a vehicle, a zoledronate, and a teriparatide group. Drugs were administered for 8 weeks in each group. Lymphocytes in the blood and thymus were analyzed and femurs were used for histological observation and lymphocytes analysis of bone marrow. Cytokines were measured in separated serum using Milliplex®multiplex immunoassay analysis.ResultsZoledronate decreased the T cell number in the bone marrow. Additionally, serum levels of interleukin (IL)-2, IL-7, IL-12, IL-15 and RANTES, which are cytokines that affect T cell activation, differentiation and/or proliferation, were significantly lower in zoledronate treated mice. Conversely, teriparatide treatment induced an increase in gamma delta T cells in peripheral blood.ConclusionGamma delta T cells in the bone marrow are expected to decrease with zoledronate treatment and increase with teriparatide treatment. If BRONJ involves a loss of gamma delta T cells in the circulation or bone marrow, then the increase in gamma delta T cells that is induced by teriparatide may account for its ability to resolve BRONJ.