TREM2 and β-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis.
TREM2 and β-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis.
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DOI：
10.4049/jimmunol.1102836
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发表时间：
2012-03-15
期刊：
影响因子：
--
通讯作者：
Colonna M
中科院分区：
文献类型：
--
作者：
Otero K;Shinohara M;Zhao H;Cella M;Gilfillan S;Colucci A;Faccio R;Ross FP;Teitelbaum SL;Takayanagi H;Colonna M
TREM 2是在破骨细胞（OC）和小胶质细胞上表达的免疫受体，其通过衔接子DAP 12传递细胞内信号。具有使TREM 2或DAP 12失活的基因突变的个体发展为Nasu-Hakola病（NHD），其具有导致骨折和早老性痴呆的骨和脑脱髓鞘的囊性样病变。这种疾病的机制知之甚少。在这里，我们报告说，TREM 2缺陷小鼠有骨质减少表型联想到NHD。在体外，TREM 2的缺乏损害破骨细胞前体（OcP）响应于巨噬细胞集落刺激因子（M-CSF）的增殖和β-连环蛋白活化。这种缺陷导致OCP加速分化为成熟OC。证实了平衡的增殖和分化的OCP的骨稳态的重要性，我们表明，在OCP中的β-连环蛋白的条件性缺失也导致减少的OCP增殖和加速破骨细胞在体外以及在体内骨质减少。这些结果表明，TREM 2调节破骨细胞生成的速率，并为NHD的骨病理学提供了机制。
TREM2 is an immunoreceptor expressed on osteoclasts (OC) and microglia that transmit intracellular signals through the adapter DAP12. Individuals with genetic mutations inactivating TREM2 or DAP12 develop the Nasu-Hakola disease (NHD) with cystic-like lesions of the bone and brain demyelination that lead to fractures and presenile dementia. The mechanism of this disease is poorly understood. Here, we report that TREM2-deficient mice have an osteopenic phenotype reminiscent of NHD. In vitro, lack of TREM2 impairs proliferation and β-catenin activation in osteoclast precursors (OcP) in response to macrophage-colony stimulating factor (M-CSF). This defect results in accelerated differentiation of OcP into mature OC. Corroborating the importance of a balanced proliferation and differentiation of OcP for bone homeostasis, we show that conditional deletion of β-catenin in OcP also results in reduced OcP proliferation and accelerated osteoclastogenesis in vitro as well as osteopenia in vivo. These results reveal that TREM2 regulates the rate of osteoclastogenesis and provide a mechanism for the bone pathology in NHD.
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影响因子：
8.7
作者：
Lanier LL
通讯作者：
Lanier LL
影响因子：
--
作者：
Kalliolias, George D.;Zhao, Baohong;Triantafyllopoulou, Antigoni;Park-Min, Kyung-Hyun;Ivashkiv, Lionel B.
通讯作者：
Ivashkiv, Lionel B.
DOI：
10.1083/jcb.200806139
发表时间：
2009-02-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mizoguchi T;Muto A;Udagawa N;Arai A;Yamashita T;Hosoya A;Ninomiya T;Nakamura H;Yamamoto Y;Kinugawa S;Nakamura M;Nakamichi Y;Kobayashi Y;Nagasawa S;Oda K;Tanaka H;Tagaya M;Penninger JM;Ito M;Takahashi N
通讯作者：
Takahashi N
影响因子：
8.7
作者：
Hamerman JA;Ni M;Killebrew JR;Chu CL;Lowell CA
通讯作者：
Lowell CA
DOI：
10.1073/pnas.0401602101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Mócsai, A;Humphrey, MB;Nakamura, MC
通讯作者：
Nakamura, MC