FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling.
FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling.
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FGFR3 缺陷通过上调 Hedgehog 信号传导导致多发软骨瘤样病变
DOI：
10.1371/journal.pgen.1005214
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发表时间：
2015-06
期刊：
影响因子：
4.5
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Zhou S;Xie Y;Tang J;Huang J;Huang Q;Xu W;Wang Z;Luo F;Wang Q;Chen H;Du X;Shen Y;Chen D;Chen L
大多数软骨性肿瘤是在骨骼发育过程中在生长板附近形成的，这表明它们是由紊乱的软骨内骨生长引起的。成纤维细胞生长因子受体（FGFR）3信号传导在此过程中起重要作用;然而，FGFR 3在软骨肿瘤发生中的作用尚不清楚。在这项研究中，我们发现，出生后软骨细胞特异性Fgfr 3缺失诱导多个软骨瘤样病变，包括内生软骨瘤和骨软骨瘤，邻近紊乱的生长板。病变显示细胞外信号调节激酶（ERK）活性降低和印度刺猬（IHH）表达增加。在Fgfr 3缺陷的原代软骨细胞中也观察到了同样的结果，其中用促分裂原活化蛋白激酶（MEK）抑制剂治疗增加了Ihh表达。重要的是，用IHH信号传导抑制剂治疗减少了Fgfr 3缺陷小鼠中软骨瘤样病变的发生。这是第一项报告FGFR 3功能丧失通过MEK/ERK信号转导下调和IHH上调导致软骨瘤样病变形成的研究，表明FGFR 3在软骨发生中具有肿瘤抑制因子样功能。
Most cartilaginous tumors are formed during skeletal development in locations adjacent to growth plates, suggesting that they arise from disordered endochondral bone growth. Fibroblast growth factor receptor (FGFR)3 signaling plays essential roles in this process; however, the role of FGFR3 in cartilaginous tumorigenesis is not known. In this study, we found that postnatal chondrocyte-specific Fgfr3 deletion induced multiple chondroma-like lesions, including enchondromas and osteochondromas, adjacent to disordered growth plates. The lesions showed decreased extracellular signal-regulated kinase (ERK) activity and increased Indian hedgehog (IHH) expression. The same was observed in Fgfr3-deficient primary chondrocytes, in which treatment with a mitogen-activated protein kinase (MEK) inhibitor increased Ihh expression. Importantly, treatment with an inhibitor of IHH signaling reduced the occurrence of chondroma-like lesions in Fgfr3-deficient mice. This is the first study reporting that the loss of Fgfr3 function leads to the formation of chondroma-like lesions via downregulation of MEK/ERK signaling and upregulation of IHH, suggesting that FGFR3 has a tumor suppressor-like function in chondrogenesis.
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影响因子：
4.5
作者：
Bowen ME;Ayturk UM;Kurek KC;Yang W;Warman ML
通讯作者：
Warman ML
DOI：
10.1038/nrm3528
发表时间：
2013-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
Foldynova-Trantirkova, Silvie;Wilcox, William R.;Krejci, Pavel
通讯作者：
Krejci, Pavel
影响因子：
64.5
作者：
Arango, NA;Lovell-Badge, R;Behringer, RR
通讯作者：
Behringer, RR
影响因子：
15.9
作者：
Chen, L;Adar, R;Deng, CX
通讯作者：
Deng, CX