Dataset Information

Knockdown of lncRNA KCNQ1OT1 suppresses the adipogenic and osteogenic differentiation of tendon stem cell via downregulating miR-138 target genes PPAR? and RUNX2.

ABSTRACT: The study aimed to investigate the mechanism and biological roles of long noncoding RNA KCNQ1OT1 in adipogenic and osteogenic differentiation of tendon stem cell. In this study, tendon injury mice model was established to detect the expression of lncRNA KCNQ1OT1, miR-138, peroxisome proliferator-activated receptor gamma (PPAR?) and runt-related gene 2 (RUNX2) using quantitative real-time PCR (qRT-PCR) and western blot. Mechanical testing was carried out to assess tendon function. Adiponectin and Osterix were used to evaluate the adipogenic and osteogenic differentiation of tendon stem cells (TSCs). The interaction between lncRNA KCNQ1OT1 and miR-138 was detected by RNA immunoprecipitation (RIP) assay and RNA pull-down assay. We found that lncRNA KCNQ1OT1, PPAR? and RUNX2 expression were significantly upregulated, while miR-138 was suppressed in tendon tissue of injured group and the separated TSCs. lncRNA KCNQ1OT1 knockdown inhibited the adipogenic and osteogenic differentiation of TSCs. Further studies indicated that lncRNA KCNQ1OT1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-138 in TSCs. Further investigations confirmed that lncRNA KCNQ1OT1 knockdown exerted anti-adipogenic and anti-osteogenic function via miR-138/PPAR? and miR-138/RUNX2 axis. Therefore, the lncRNA KCNQ1OT1/miR-138/PPAR? or RUNX2 axis modulated adipogenic and osteogenic differentiation of tendon stem cell, which might be a promising therapeutic target for tendon injuries.

SUBMITTER: Yu Y

PROVIDER: S-EPMC6237432 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Knockdown of lncRNA KCNQ1OT1 suppresses the adipogenic and osteogenic differentiation of tendon stem cell via downregulating miR-138 target genes PPARγ and RUNX2.

Yu Yang Y Chen Ying Y Zhang Xiaolei X Lu Xiaolang X Hong Jianjun J Guo Xiaoshan X Zhou Dongsheng D

Cell cycle (Georgetown, Tex.) 20181025 19-20

The study aimed to investigate the mechanism and biological roles of long noncoding RNA KCNQ1OT1 in adipogenic and osteogenic differentiation of tendon stem cell. In this study, tendon injury mice model was established to detect the expression of lncRNA KCNQ1OT1, miR-138, peroxisome proliferator-activated receptor gamma (PPARγ) and runt-related gene 2 (RUNX2) using quantitative real-time PCR (qRT-PCR) and western blot. Mechanical testing was carried out to assess tendon function. Adiponectin and ...[more]

PMID: 30321077

Similar Datasets

Project description:In many skeletal diseases, including osteoporosis and disuse osteopenia, defective osteoblast differentiation is associated with increased marrow adipogenesis. The relative activity of two transcription factors, RUNX2 and PPARγ, controls whether a mesenchymal cell will differentiate into an osteoblast or adipocyte. Herein we show that the ERK/MAP kinase pathway, an important mediator of mechanical and hormonal signals in bone, stimulates osteoblastogenesis and inhibits adipogenesis via phosphorylation of RUNX2 and PPARγ. Induction of osteoblastogenesis in ST2 mesenchymal cells was associated with increased MAPK activity and RUNX2 phosphorylation. Under these conditions PPARγ phosphorylation also increased, but adipogenesis was inhibited. In contrast, during adipogenesis MAPK activity and phosphorylation of both transcription factors was reduced. RUNX2 phosphorylation and transcriptional activity were directly stimulated by MAPK, a response requiring phosphorylation at S301 and S319. MAPK also inhibited PPARγ-dependent transcription via S112 phosphorylation. Stimulation of MAPK increased osteoblastogenesis and inhibited adipogenesis, while dominant-negative suppression of activity had the opposite effect. In rescue experiments using Runx2(-/-) mouse embryo fibroblasts (MEFs), wild type or, to a greater extent, phosphomimetic mutant RUNX2 (S301E,S319E) stimulated osteoblastogenesis while suppressing adipogenesis. In contrast, a phosphorylation-deficient RUNX2 mutant (S301A,S319A) had reduced activity. Conversely, wild type or, to a greater extent, phosphorylation-resistant S112A mutant PPARγ strongly stimulated adipogenesis and inhibited osteoblastogenesis in Pparg(-/-) MEFs, while S112E mutant PPARγ was less active. Competition between RUNX2 and PPARγ was also observed at the transcriptional level. Together, these studies highlight the importance of MAP kinase signaling and RUNX2/PPARγ phosphorylation in the control of osteoblast and adipocyte lineages.

Dataset Information

Knockdown of lncRNA KCNQ1OT1 suppresses the adipogenic and osteogenic differentiation of tendon stem cell via downregulating miR-138 target genes PPAR? and RUNX2.

Publications

Knockdown of lncRNA KCNQ1OT1 suppresses the adipogenic and osteogenic differentiation of tendon stem cell via downregulating miR-138 target genes PPARγ and RUNX2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets