DLX5 and HOXC8 enhance the chondrogenic differentiation potential of stem cells from apical papilla via LINC01013

被引：36

作者：

Yang, Haoqing ^{[1
]}

Cao, Yangyang ^{[1
]}

Zhang, Jianpeng ^{[2
]}

Liang, Yuncun ^{[1
]}

Su, Xiaomin ^{[1
]}

Zhang, Chen ^{[1
]}

Liu, Huina ^{[1
]}

Han, Xiao ^{[1
]}

Ge, Lihua ^{[1
]}

Fan, Zhipeng ^{[1
]}

机构：

[1] Capital Med Univ, Sch Stomatol, Beijing Stomatol Hosp, Beijing Key Lab Tooth Regenerat & Funct Reconstru, 4 Tian Tan Xi Li, Beijing 100050, Peoples R China

[2] Capital Med Univ, Beijing Stomatol Hosp, Sch Stomatol, Dept Endodont, Beijing 100050, Peoples R China

来源：

STEM CELL RESEARCH & THERAPY | 2020年 / 11卷 / 01期

基金：

中国国家自然科学基金;

关键词：

DLX5; HOXC8; Chondrogenic differentiation; Stem cells from apical papilla (SCAPs); LncRNA; LONG NONCODING RNA; BONE-MARROW; CHONDROCYTE DIFFERENTIATION; KNEE OSTEOARTHRITIS; CARTILAGE REPAIR; EXPRESSION; GENES; DEGRADATION; HOMEOSTASIS; SYSTEM;

D O I：

10.1186/s13287-020-01791-8

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background Mesenchymal stem cell (MSC)-based cartilage tissue regeneration is a treatment with great potential. How to enhance the MSC chondrogenic differentiation is a key issue involved in cartilage formation. In the present study, we seek to expound the phenotypes and mechanisms of DLX5 in chondrogenic differentiation function in MSCs. Methods Stem cells from apical papilla (SCAPs) were used. The Alcian Blue staining, pellet culture system, and cell transplantation in rabbit knee cartilage defect were used to evaluate the chondrogenic differentiation function of MSCs. Western blot, real-time RT-PCR, and ChIP assays were used to evaluate the molecular mechanisms. Results DLX5 and HOXC8 expressions were upregulated during chondrogenic differentiation. In vitro results showed that DLX5 and HOXC8 enhanced the expression of chondrogenic markers including collagen II (COL2), collagen V (COL5), and sex-determining region Y box protein 9 (SOX9) and promoted the chondrogenic differentiation and the formation of cartilage clumps in the pellet culture system. Mechanically, DLX5 and HOXC8 formed protein complexes and negatively regulated the LncRNA, LINC01013, via directly binding its promoter. In vivo transplantation experiment showed that DLX5 and HOXC8 could restore the cartilage defect in the rabbit knee model. In addition, knock-down of LINC01013 enhanced the chondrogenic differentiation of SCAPs. Conclusions In conclusion, DLX5 and HOXC8 enhance the chondrogenic differentiation abilities of SCAPs by negatively regulating LINC01013 in SCAPs, and provided the potential target for promoting cartilage tissue regeneration.

引用

页数：16

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