LITTIP/Lgr6/HnRNPK复合体通过Wnt信号调控骨水泥形成。

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-08-09 DOI:10.1038/s41368-023-00237-0
Tiancheng Li, Han Wang, Yukun Jiang, Shuo Chen, Danyuan Huang, Zuping Wu, Xing Yin, Chenchen Zhou, Yuyu Li, Shujuan Zou
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引用次数: 0

摘要

正畸诱导牙根吸收(OIRR)是正畸治疗中的一个严重并发症。刺激骨水泥修复是治疗OIRR的基本方法。甲状旁腺激素(PTH)可能是治疗OIRR的潜在药物,但其作用仍缺乏直接证据,其潜在机制尚不清楚。本研究旨在探索长链非编码rna (lncRNAs)在介导间歇性甲状旁腺激素的合成代谢作用和促进骨质修复中的潜在参与,因为确定lncrna与疾病的关联可以为疾病的诊断和治疗提供有价值的见解。在这里,我们发现间歇性PTH通过调节Wnt通路调节永生化小鼠成水泥细胞OCCM-30的细胞增殖和矿化。在体内,每天给药PTH足以通过局部抑制Wnt/β-catenin信号传导来加速根再生。通过RNA芯片分析,鉴定出lncRNA LITTIP(间歇性PTH下LGR6基因间转录物)是间歇性PTH下骨水泥形成的关键调控因子。通过RNA纯化(ChIRP)和RNA免疫沉淀(RIP)分离染色质发现,LITTIP与富含亮氨酸的重复g蛋白偶联受体6 (LGR6)和异质核核糖核蛋白K (HnRNPK)蛋白的mRNA结合。进一步共转染实验证实,LITTIP在LITTIP/Lgr6/HnRNPK复合物的形成中发挥了结构作用。此外,LITTIP能够通过rna结合蛋白HnRNPK促进LGR6的表达。总的来说,我们的研究结果表明间歇性PTH通过抑制Wnt途径加速根再生。lncRNA LITTIP通过HnRNPK促进LGR6的高表达激活Wnt/β-catenin信号通路,负向调控骨水泥形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling.

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.

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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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