Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Center of Stomatology and National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.
Department of Periodontics, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin 300041, China.
Cells. 2022 Sep 1;11(17):2729. doi: 10.3390/cells11172729.
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.
恒牙迟萌是颅锁骨发育不全（CCD）的常见症状。先前的研究集中在 Runt 相关转录因子 2 基因（RUNX2）突变导致的成骨异常上。然而，CCD 中破骨细胞生成和骨吸收的缺陷以及长链非编码（lnc）RNAs 介导的表观遗传调控仍有待阐明。在这里，在转染 RUNX2 突变表达盒的 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 可通过竞争性结合 microRNA（miR）-221-5p 来正向调节破骨细胞生成和骨吸收。OC-lncRNA 促进 CXC 趋化因子受体 3（CXCR3）的表达。CXC 趋化因子配体 10（CXCL10）与核因子-κB 之间的相互作用构成了一个正反馈，正向调节破骨细胞生成和骨吸收。这些结果表明，OC-lncRNA 通过 OC-lncRNA-miR-221-5p-CXCR3 轴介导破骨细胞功能障碍，参与 CCD 中恒牙迟萌的过程。
