Retracted: Long noncoding RNA ZBED3‐AS1 induces the differentiation of mesenchymal stem cells and enhances bone regeneration by repressing IL‐1β via Wnt/β‐catenin signaling pathway

Abstract

Bone regeneration, as a physiological process of bone formation, is regulated by multiple cytokines. Long noncoding RNAs are involved in the progress of bone formation. The present study investigated role by which ZBED3‐AS1 acts to control the differentiation of mesenchymal stem cells (MSCs) and bone regeneration. Bioinformatics prediction and dual luciferase reporter gene assay identified putative ZBED3‐AS1 binding sites on the 3′‐untranslated region of interleukin‐1β (IL‐1β). Then, RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that ZBED3‐AS1 could regulate the expression of IL‐1β by binding to the transcription factor CREB. Notably, ZBED3‐AS1 was shown to negatively regulate IL‐1β expression. After model establishment in rats simulating bone injury, MSCs were isolated and delivered with ZBED3‐AS1, Si‐ZBED3‐AS1, Si‐IL‐1β, or DKK (inhibitor of Wnt/β‐catenin signaling pathway) to identify their roles in osteogenic differentiation by evaluating MSC colony formation and proliferation. Then, number of mineralized nodules, alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression, and expression of osteogenesis‐related genes were determined. Overexpression of ZBED3‐AS1 or silencing of IL‐1β was shown to accelerate ectopic osteogenesis, as reflected by increasing the number of mineralized nodules, ALP activity, and OCN expression, and promoting MSC colony formation and proliferation. Additionally, ZBED3‐AS1 activated the Wnt/β‐catenin signaling pathway by negatively regulating IL‐1β. IL‐1β inhibited osteogenic differentiation by suppressing the Wnt/β‐catenin signaling pathway. Furthermore, the effect of ZBED3‐AS1 and IL‐1β on osteogenic differentiation was confirmed in vivo. Taken together, upregulation of ZBED3‐AS1 could restore differentiation of MSCs and enhance bone regeneration via activation of Wnt/β‐catenin signaling pathway by repressing IL‐1β.

lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

“…lncRNAs, a class of >200 nucleotides non-coding RNAs, was reported to be involved in various progression of disease including osteoporosis [34][35][36]. For example, Yang et al showed that lncRNA ORLNC1 involved in osteoporosis via regulating BMSCs osteogenic and adipogenic differentiation [37].…”

A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p–PIK3R1 axis

“…Some scholars also focused on the RNA modification of BMSCs. However, as mentioned, all previous studies used inducers to treat BMSCs in vitro to search for novel lncRNAs, or referred to well-known lncRNAs studied in other diseases 43 , which might be insufficient to simulate the actual changes in vivo. The OVX rat model has been widely accepted for the study of postmenopausal osteoporosis, which is approved by the US Food and Drug Administration (FDA) 44 .…”

Non-Coding RNAs in Cartilage Development: An Updated Review

“…Then, another study confirmed that this lncRNA’s expression fluctuates during the chondrogenic differentiation of human synovial fluid-derived MSCs (SFMSCs) [132]. Further complementary studies have verified that the forced expression of this lncRNA enhances the chondrogenic potential by regulating the Wnt/β-catenin signaling pathway via the upregulation of zbed3 [138].…”