All-trans retinoic acid inhibits the osteogenesis of periodontal ligament stem cells by promoting IL-1 beta production via NF-Kappa B signaling

作者全名："Guo, Li; Zhang, Yan; Liu, Honghong; Cheng, Qianyu; Yang, Shiyao; Yang, Deqin"

作者地址："[Guo, Li; Zhang, Yan; Liu, Honghong; Cheng, Qianyu; Yang, Shiyao; Yang, Deqin] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Stomatol Hosp, Chongqing 404100, Peoples R China; [Guo, Li; Zhang, Yan; Liu, Honghong; Cheng, Qianyu; Yang, Shiyao; Yang, Deqin] Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing 404100, Peoples R China"

通信作者："Yang, DQ (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Stomatol Hosp, Chongqing 404100, Peoples R China.; Yang, DQ (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing 404100, Peoples R China."

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000802904700003

JCR分区：Q1

影响因子：5.6

年份：2022

卷号：108

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：All-trans retinoic acid; Periodontal ligament stem cells; Osteogenic differentiation; IL-1?; NF; ?B signaling; NLRP3 inflammasome

摘要："All-trans retinoic acid (ATRA), a main derivative of vitamin A, has been shown to affect the osteogenic differentiation of mesenchymal stem cells (MSCs). Periodontal ligament stem cells (PDLSCs) possess characteristics of MSC and show strong potential for use in periodontal tissue restoration. However, the effect of ATRA on the osteogenic differentiation of PDLSCs remains unclear. In this study, we explored the effect of ATRA on the PDLSCs osteogenic differentiation. PDLSCs were harvested from the periodontal membrane and treated with or without ATRA. CCK-8 and cell cycle analysis were used to evaluate PDLSC proliferation. PDLSC migration was assessed by scratch tests. qRT-PCR, western blotting, alkaline phosphatase staining, alizarin red staining and calcium quantification were performed to estimate the PDLSCs osteogenic differentiation capability and RNA sequencing to select differentially expressed genes (DEGs). Expression and activation of signaling elements were assessed by qRT-PCR, western blotting and immunofluorescence. Finally, we discovered that ATRA repressed the migration, proliferation, and osteogenesis ability of PDLSCs. RNA sequencing revealed 493 DEGs. Levels of interleukin-1 beta (IL-1 beta) were increased at varied time points after ATRA treatment. The inhibitive influence of ATRA on the osteogenesis of PDLSCs was partially reversed after neutralizing IL-1 beta. In addition, IL-1 beta levels were significantly attenuated by nuclear factor-kappa B (NF-kappa B) inhibitor BAY11-7082 and NLRP3 inhibitor MCC950. Taken together, our results demonstrate that ATRA disrupts the osteogenesis and mineralization of PDLSCs by promoting IL-1 beta expression via activating NF-kappa B signaling and NLRP3 inflammasome, which may offer a new method for improving the ATRA-induced disruption of osteoblast differentiation."

基金机构："National Natural Scientific Foundation of China [31970783]; Operative Dentistry and Endodontics, Chongqing Key Medical Discipline Construction Project [55]"

基金资助正文："This research was financed by the National Natural Scientific Foundation of China (No. 31970783) , and Operative Dentistry and Endodontics, Chongqing Key Medical Discipline Construction Project (2011, NO.55) ."