Wnt/beta-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

作者全名："Yao, Xin-Tong; Li, Pei-pei; Liu, Jiang; Yang, Yuan-Yuan; Luo, Zhen-Ling; Jiang, Hai-Tao; He, Wen-Ge; Luo, Hong-Hong; Deng, Yi-Xuan; He, Bai-Cheng"

作者地址："[Yao, Xin-Tong; Li, Pei-pei; Yang, Yuan-Yuan; Luo, Hong-Hong; Deng, Yi-Xuan; He, Bai-Cheng] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Yao, Xin-Tong; Li, Pei-pei; Yang, Yuan-Yuan; Luo, Hong-Hong; Deng, Yi-Xuan; He, Bai-Cheng] Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Liu, Jiang] Dalian Med Univ, Dalian 116044, Liaoning, Peoples R China; [Liu, Jiang] 960th Hosp PLA Joint Logist Support Force, Dept Orthoped, Jinan 250013, Shandong, Peoples R China; [Luo, Zhen-Ling] Taizhou Food Inspect Ctr, Taizhou 318000, Zhejiang, Peoples R China; [Jiang, Hai-Tao; He, Wen-Ge] Chongqing Med Univ, Dept Orthopaed, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："He, BC (通讯作者)，Chongqing Med Univ, Coll Pharm, Dept Pharmacol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; He, BC (通讯作者)，Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China."

来源：TISSUE ENGINEERING AND REGENERATIVE MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000963706600001

JCR分区：Q2

影响因子：4.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Cyp26b1; Bone regeneration; Mesenchymal stem cells; Osteogenic differentiation; Wnt/b-catenin signalling

摘要："BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC-MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro-computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering."

基金机构：National Natural Science Foundation of China (NSFC); National Key Research and Development Program of China [81572226]; [2016YFC1000803]

基金资助正文："Thanks to Prof. Tongchuan He (the medical center of the University of Chicago) for his generous provision of the cells, recombinant adenoviruses, and pAdtrace361 plasmid of the recombinant adenoviruses. This work was supported by the National Natural Science Foundation of China (NSFC, 81572226), and the National Key Research and Development Program of China. This work was supported by the National Natural Science Foundation of China (NSFC, 81572226), and the National Key Research and Development Program of China (2016YFC1000803)."