TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells.
TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells.
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DOI：
10.1186/ar2038
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发表时间：
2006
影响因子：
4.9
通讯作者：
Nakao A
中科院分区：
文献类型：
--
作者：
Ando T;Ichikawa J;Wako M;Hatsushika K;Watanabe Y;Sakuma M;Tasaka K;Ogawa H;Hamada Y;Yagita H;Nakao A
肿瘤坏死因子样弱诱导因子是肿瘤坏死因子家族的一员，是一种多功能细胞因子，主要通过其受体成纤维细胞生长因子诱导14(Fn14)来调节细胞的生长、迁移和存活。然而，它在骨骼中的生理作用在很大程度上是未知的。在此，我们报道了TWEE对小鼠成骨细胞MC3T3-E1的各种作用。经PI3K-AKT调节刺激后，MC3T3-E1细胞表达Fn14并产生RANTES(激活后调节，健康T细胞表达和分泌)，但不产生核因子-κB(NF-κB)途径。此外，TWAKE还通过丝裂原活化蛋白激酶(MAPK)ERK通路抑制骨形态发生蛋白-2(BMP-2)诱导的成骨细胞分化标志物碱性磷酸酶的表达。此外，TWeak还通过MAPKERK信号转导通路上调了κB配体受体活化蛋白的表达。TWEK对MC3T3-E1细胞的上述作用可被小鼠Fn14-Fc嵌合体所消除。我们还分别在成骨细胞系和破骨细胞系细胞系或小鼠骨组织中发现了显著的TWEK mRNA或蛋白表达。最后，我们发现人成骨细胞表达Fn14，并在TWINE刺激下诱导RANTES和RANKL。总之，TWEEP/Fn14相互作用调节MC3T3-E1细胞RANTES的产生、BMP-2诱导的分化和RANKL的表达。因此，TWAGE可能是一种新的细胞因子，调节成骨细胞功能的几个方面。
Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of the TNF family, is a multifunctional cytokine that regulates cell growth, migration, and survival principally through a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14). However, its physiological roles in bone are largely unknown. We herein report various effects of TWEAK on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed Fn14 and produced RANTES (regulated upon activation, healthy T cell expressed and secreted) upon TWEAK stimulation through PI3K-Akt, but not nuclear factor-κB (NF-κB), pathway. In addition, TWEAK inhibited bone morphogenetic protein (BMP)-2-induced expression of osteoblast differentiation markers such as alkaline phosphatase through mitogen-activated protein kinase (MAPK) Erk pathway. Furthermore, TWEAK upregulated RANKL (receptor activation of NF-κB ligand) expression through MAPK Erk pathway in MC3T3-E1 cells. All these effects of TWEAK on MC3T3-E1 cells were abolished by mouse Fn14-Fc chimera. We also found significant TWEAK mRNA or protein expression in osteoblast – and osteoclast-lineage cell lines or the mouse bone tissue, respectively. Finally, we showed that human osteoblasts expressed Fn14 and induced RANTES and RANKL upon TWEAK stimulation. Collectively, TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in MC3T3-E1 cells. TWEAK may thus be a novel cytokine that regulates several aspects of osteoblast function.
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DOI：
10.1083/jcb.96.1.191
发表时间：
1983-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sudo H;Kodama HA;Amagai Y;Yamamoto S;Kasai S
通讯作者：
Kasai S
影响因子：
3.5
作者：
De Ketelaere, A;Vermeulen, L;Moelans, I
通讯作者：
Moelans, I
影响因子：
4
作者：
REDDI, AH
通讯作者：
REDDI, AH
DOI：
10.1161/01.atv.0000062883.93715.37
发表时间：
2003-04-01
影响因子：
8.7
作者：
Donohue, PJ;Richards, CM;Winkles, JA
通讯作者：
Winkles, JA
影响因子：
4.4
作者：
Kanamaru, Y;Sumiyoshi, K;Nakao, A
通讯作者：
Nakao, A