A Novel lncRNA Mediates the Delayed Tooth Eruption of Cleidocranial Dysplasia.
A Novel lncRNA Mediates the Delayed Tooth Eruption of Cleidocranial Dysplasia.
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作者：
恒牙延迟萌出是锁骨颅骨发育不良（CCD）的常见症状。以前的研究集中在由Runt相关转录因子-2基因（RUNX 2）突变引起的骨生成异常。然而，破骨细胞生成和骨吸收的缺陷，以及CCD中长链非编码（lnc）RNA介导的表观遗传调控仍有待阐明。在这里，在用RUNX 2突变表达盒转染的RAW 264.7细胞的破骨细胞分化过程中鉴定出一种新型破骨细胞特异性lncRNA（OC-lncRNA）。我们进一步证实OC-lncRNA正调控破骨细胞生成和骨吸收。OC-lncRNA通过竞争性结合microRNA（miR）-221-5p促进CXC趋化因子受体3型（CXCR 3）的表达。CXCR 3-CXC基序趋化因子配体10（CXCL 10）相互作用和核因子-κB构成正反馈，正调节破骨细胞生成和骨吸收。这些结果表明，OC-lncRNA介导的破骨细胞功能障碍通过OC-lncRNA-miR-221- 5 p-CXCR 3轴，其参与CCD的延迟牙齿萌出的过程。
Delayed eruption of permanent teeth is a common symptom of cleidocranial dysplasia (CCD). Previous studies have focused on the anomaly of osteogenesis resulting from mutations in the Runt-related transcription factor-2 gene (RUNX2). However, deficiencies in osteoclastogenesis and bone resorption, and the epigenetic regulation mediated by long non-coding (lnc)RNAs in CCD remain to be elucidated. Here, a novel osteoclast-specific lncRNA (OC-lncRNA) was identified during the osteoclast differentiation of RAW 264.7 cells transfected with a RUNX2 mutation expression cassette. We further confirmed that OC-lncRNA positively regulated osteoclastogenesis and bone resorption. The OC-lncRNA promoted the expression of CXC chemokine receptor type 3 (CXCR3) by competitively binding to microRNA (miR)-221-5p. The CXCR3–CXC-motif chemokine ligand 10 (CXCL10) interaction and nuclear factor-κB constituted a positive feedback that positively regulated osteoclastogenesis and bone resorption. These results demonstrate that OC-lncRNA-mediated osteoclast dysfunction via the OC-lncRNA–miR-221-5p–CXCR3 axis, which is involved in the process of delayed tooth eruption of CCD.
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影响因子：
2.1
作者：
Impellizzeri A;Midulla G;Romeo U;La Monaca C;Barbato E;Galluccio G
通讯作者：
Galluccio G
影响因子：
--
作者：
Kwak, Han Bok;Ha, Hyunil;Lee, Zang Hee
通讯作者：
Lee, Zang Hee
影响因子：
11.2
作者：
Lee, Jong-Ho;Kim, Ha-Neui;Lee, Zang Hee
通讯作者：
Lee, Zang Hee
DOI：
10.1111/j.1749-6632.2009.04813.x
发表时间：
2009-01-01
期刊：
CONTEMPORARY CHALLENGES IN AUTOIMMUNITY
影响因子：
--
作者：
Lacotte, Stephanie;Brun, Susana;Dumortier, Helene
通讯作者：
Dumortier, Helene
破骨细胞分化中的 LncRNA-mRNA 表达谱和功能网络
影响因子：
5.3
作者：
Liu W;Li Z;Cai Z;Xie Z;Li J;Li M;Cen S;Tang S;Zheng G;Ye G;Su H;Wang S;Wang P;Shen H;Wu Y
通讯作者：
Wu Y