CircRNA FAT1 Regulates Osteoblastic Differentiation of Periodontal Ligament Stem Cells via miR-4781-3p/SMAD5 Pathway

Abstract

The ability of human periodontal ligament stem cells (PDLSCs) to differentiate into osteoblasts is significant in periodontal regeneration tissue engineering. In this study, we explored the role and mechanism of circRNA FAT1 (circFAT1) in the osteogenic differentiation of human PDLSCs. The proliferation capacity of PDLSCs was evaluated by EdU and CCK-8 assay. The abilities of circFAT1 and miR-4781-3p in regulating PDLSC differentiation were analyzed by western blot, reverse transcription-polymerase chain reaction (RT-PCR), alkaline phosphatase (ALP), and Alizarin red staining (ARS). A nucleocytoplasmic separation experiment was utilized for circFAT1 localization. A dual-luciferase reporter assay confirmed the binding relationship between miR-4781-3p and circFAT1. It was showed that circFAT1 does not affect the proliferation of PDLSCs. The osteogenic differentiation of PDLSCs was benefited from circFAT1, which serves as a miRNA sponge for miR-4781-3p targeting SMAD5. Both knockdown of circFAT1 and overexpression of miR-4781-3p suppressed the osteogenic differentiation of PDLSCs. Thus, circFAT1 might be considered as a potential target of PDLSCs mediated periodontal bone regeneration.

Circular RNA BIRC6 depletion promotes osteogenic differentiation of periodontal ligament stem cells via the miR-543/PTEN/PI3K/AKT/mTOR signaling pathway in the inflammatory microenvironment

“…For instance, the expression profile of circRNAs was found to be significantly changed during PDLSC osteogenic differentiation [ 9 ]. Ye et al [ 10 ] reported that circFAT1 depletion suppressed the osteogenic differentiation of PDLSCs in vitro and bone formation in vivo, suggesting that circFAT1 might be a potential candidate regulator of PDLSC osteogenesis. Similarly, the expression level of CDR1as was significantly increased during osteogenic differentiation of PDLSCs.…”

MicroRNA-28-5p as a potential diagnostic biomarker for chronic periodontitis and its role in cell proliferation and inflammatory response

“…Chronic periodontitis (CP) is a devastating chronic inflammatory disease caused by the dysbiosis of the oral flora that affects 90% of the world's population. 1 , 2 Inflammation stimulates the dissolution of collagen fibers of the periodontal ligament and reduces periodontal attachment, resulting in alveolar bone resorption and root exposure, thus causing tooth loosening and loss. 3 Current methods of diagnosis of CP are clinical examination and imaging, but they are expensive, and most patients are diagnosed only when the severity of CP increases or even when they lose teeth, which imposes a serious burden on their lives.…”

miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1

“…Human PDLSCs were all purchased from BeNa culture collection as previously described [ 26 ]. PDLSCs were incubated in Dulbecco’s modified Eagle medium (DMEM) (Sigma, USA) containing 10% fetal bovine serum (FBS) (Hyclone, GE Healthcare Life Sciences, Logan, UT, USA) in a constant temperature incubator (37 °C) with 5% CO 2 .…”