LncRNA KCNQ1OT1 promotes osteogenic differentiation to relieve osteolysis via Wnt/β-catenin activation

Abstract

BackgroundResveratrol (RSV) has been reported to stimulate osteoblast differentiation in which Wnt/β-catenin signaling pathway played a crucial role. However, whether and how RSV activated Wnt/β-catenin pathway in osteogenic differentiation still remained elusive.MethodsIn vivo polymethylmethacrylate (PMMA) particle-induced osteolysis (PIO) mouse model and in vitro PMMA particle-stimulated mouse mesenchymal stem cells (mMSCs) experiments were established. Relative expression levels of lncRNA KCNQ1OT1, β-catenin, Runx2, Osterix and osteocalcin were determined using quantitative Real-Time PCR. Western blotting was used to measure β-catenin protein expression. In addition, the alkaline phosphatase activity and mineral deposition level using alizarin red S staining were performed to examine osteogenic differentiation status. The interaction between KCNQ1OT1 and β-catenin was confirmed by RNA pull down assay.ResultsRSV significantly attenuated PIO in vivo and PMMA-particle inhibition of osteogenic differentiation of mMSCs. Moreover, KCNQ1OT1 exerted the similar function in mMSCs by regulating β-catenin. Further study demonstrated that RSV exerted its effect on osteoblastic differentiation by regulating KCNQ1OT1. Consequently, RSV alleviated PMMA-particle inhibition of osteoblastic differentiation via Wnt/β-catenin pathway activation in vivo and in vitro.ConclusionRSV accelerated osteoblast differentiation by regulating lncRNA KCNQ1OT1 via Wnt/β-catenin pathway activation, indicating the functional role of RSV in modulating osteogenesis.

Retracted Article: Long non-coding RNA KCNQ1OT1 promotes osteosarcoma progression by increasing β-catenin activity

“…[25][26][27][28] Previous research demonstrated that KCNQ1OT1 increases beta-catenin protein level and its transcriptional activity in osteoblast cells. 16 We investigated in the present research whether KCNQ1OT1 was involved in osteosarcoma development. Our data for the rst time demonstrated a signicant increase in KCNQ1OT1 expression level in osteosarcoma and its association with osteosarcoma progression.…”

“…14,15 A previous research by Gao et al demonstrated that overexpressing KCNQ1OT1 in osteoblast cells might increase beta-catenin expression and its activity, presumably by binding to beta-catenin. 16 Beta-catenin is a transcription co-activator, complexing with TCF/LEF family transcription factors to activate the transcription of target genes such as MYC, JUN, WISP1 and CCND1 that are involved in cell proliferation, survival and mobility. 17,18 Activation of WNT/beta-catenin signaling pathway has been demonstrated to promote osteosarcoma cell proliferation, metastasis and chemoresistance, and inhibition of this osteosarcoma-promoting pathway might synergize with current therapeutic approaches and improve patients' outcome.…”

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

“…Furthermore, JNK is closely related to the reorganization of the actin cytoskeleton, which is essential for chondrogenic differentiation (24). Other investigations reported that β‐catenin‐related signaling pathways, such as the canonical Wnt/ β‐catenin and PI3K/Akt/GSK‐3β/β‐catenin pathways, are involved in the osteogenic differentiation of MSCs (25, 26). On the basis of this evidence, it is reasonable to deduce that the up‐regulation of phospho‐JNK and suppression of β‐catenin may be closely associated with the prochondrogenic and antiossific effects of KGN preconditioning.…”

Tanshinone IIA protects lens epithelial cells from H2O2‐induced injury by upregulation of lncRNA ANRIL

“…Besides, lncRNAs are pivotal regulatory molecules that are involved in diverse biological processes, including cell proliferation, cell-cycle progression, epithelial-mesenchymal transition (Cen et al, 2018), apoptosis (Y. Guo, Hu, Hu, He, & Li, 2018), differentiation (Gao, Ge, Li, Zhou, & Xu, 2018), and chromosome inactivation (Yue & Ogawa, 2018 (Hu, Jiang, & Jiang, 2017). Besides, the importance of lncRNA ANRIL in other diseases, like atherosclerosis (Chi et al, 2017) and diabetic retinopathy (Thomas, Feng, & Chakrabarti, 2017), have also been gradually reported.…”