Melatonin Regulates Osteoblast Differentiation Through the M6A Reader HnRNPA2B1 Under Simulated Microgravity

Overview

Journal Curr Issues Mol Biol

Publisher MDPI

Specialty Molecular Biology

Date 2024 Sep 27

PMID 39329924

Authors

Quan Sun

Liqun Xu

Zebing Hu

Jingchun Liu

Tingfei Yu

Meng Li

Shu Zhang

Fei Shi

Affiliations

Soon will be listed here.

Abstract

Recent studies have confirmed that melatonin and N6-methyladenosine (m6A) modification can influence bone cell differentiation and bone formation. Melatonin can also regulate a variety of biological processes through m6A modification. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) serves as a reader of m6A modification. In this study, we used the hindlimb unloading model as an animal model of bone loss induced by simulated microgravity and used 2D clinorotation to simulate a microgravity environment for cells on the ground. We found that hnRNPA2B1 was downregulated both in vitro and in vivo during simulated microgravity. Further investigations showed that hnRNPA2B1 could promote osteoblast differentiation and that overexpression of hnRNPA2B1 attenuated the suppression of osteoblast differentiation induced by simulated microgravity. We also discovered that melatonin could promote the expression of hnRNPA2B1 under simulated microgravity. Moreover, we found that promotion of osteoblast differentiation by melatonin was partially dependent on hnRNPA2B1. Therefore, this research revealed, for the first time, the role of the melatonin/hnRNPA2B1 axis in osteoblast differentiation under simulated microgravity. Targeting this axis may be a potential protective strategy against microgravity-induced bone loss and osteoporosis.

Citing Articles

Melatonin antagonizes bone loss induced by mechanical unloading via IGF2BP1-dependent mA regulation.

Xu L, Zhang L, Sun Q, Zhang X, Zhang J, Zhao X Cell Mol Life Sci. 2025; 82(1):60.

PMID: 39849105 PMC: 11757843. DOI: 10.1007/s00018-025-05588-x.

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