The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability

نویسندگان

چکیده

AlkB homolog 5 (ALKBH5) has been reported as a key m6A demethylase that is involved in development and diseases; however, the function of ALKBH5 osteogenesis remains unknown. In this study, we report mRNA protein expression were upregulated during osteoblast differentiation knockdown suppressed differentiation, mineralization, osteogenic biomarkers. Conversely, overexpression promoted osteogenesis. Moreover, wild-type ALKBH5, but not m6A-modified active site mutant could rescue knockdown-induced inhibition. Furthermore, significantly impaired stability transcription factor Runx2, which plays role differentiation. Taken together, our results suggest promotes through modulating Runx2 stability.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

miR‑142‑3p promotes osteoblast differentiation by modulating Wnt signaling.

Canonical Wnt signaling is critical for the control of osteoblast differentiation in human mesenchymal stem cells. MicroRNAs (miRs) are essential regulators of cell differentiation by post‑transcriptional regulation of target gene expression. The aim of the present study was to investigate the molecular mechanism by which miR‑142‑3p promotes osteoblastic differentiation using the human fetal os...

متن کامل

CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation

Runx2, an essential transactivator for osteoblast differentiation, is tightly regulated at both the transcriptional and posttranslational levels. In this paper, we report that CHIP (C terminus of Hsc70-interacting protein)/STUB1 regulates Runx2 protein stability via a ubiquitination-degradation mechanism. CHIP interacts with Runx2 in vitro and in vivo. In the presence of increased Runx2 protein...

متن کامل

Histone demethylase Jmjd3 regulates osteoblast differentiation via transcription factors Runx2 and osterix.

Post-translational modifications of histones including methylation play important roles in cell differentiation. Jumonji domain-containing 3 (Jmjd3) is a histone demethylase, which specifically catalyzes the removal of trimethylation of histone H3 at lysine 27 (H3K27me3). In this study, we examined the expression of Jmjd3 in osteoblasts and its roles in osteoblast differentiation. Jmjd3 express...

متن کامل

Epigenetic silencing of HDAC1 by miR-449a upregulates Runx2 and promotes osteoblast differentiation.

Human-induced pluripotent (iPS) cells can be induced to differentiate into osteoblasts, but the process is inefficient and time-consuming. Previous studies indicated a close association between the expression of Runx2 and osteoblast differentiation, and established that the transcriptional activation of the Runx2 gene was closely associated with histone acetylation. microRNA-449a (miR-449a) rep...

متن کامل

GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2

Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteoge...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: FEBS Letters

سال: 2021

ISSN: ['0014-5793', '1873-3468']

DOI: https://doi.org/10.1002/1873-3468.14145