Long non-coding RNA (LncRNA) HOTAIR regulates BMP9-induced osteogenic differentiation by targeting the proliferation of mesenchymal stem cells (MSCs).

Content Provider	Europe PMC
Author	Li, Ruidong Zhang, Wenwen Yan, Zhengjian Liu, Wei Fan, Jiaming Feng, Yixiao Zeng, Zongyue Cao, Daigui Haydon, Rex C. Luu, Hue H. Deng, Zhong-Liang He, Tong-Chuan Zou, Yulong
Abstract	Long non-coding RNAs are important regulators of biological processes, but their roles in the osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. Here we investigated the role of murine HOX transcript antisense RNA (mHotair) in BMP9-induced osteogenic differentiation of MSCs using immortalized mouse adipose-derived cells (iMADs). Touchdown quantitative polymerase chain reaction analysis found increased mHotair expression in bones in comparison with most other tissues. Moreover, the level of mHotair in femurs peaked at the age of week-4, a period of fast skeleton development. BMP9 could induce earlier peak expression of mHotair during in vitro iMAD osteogenesis. Silencing mHotair diminished BMP9-induced ALP activity, matrix mineralization, and expression of osteogenic, chondrogenic and adipogenic markers. Cell implantation experiments further confirmed that knockdown of mHotair attenuated BMP9-induced ectopic bone formation and mineralization of iMADs, leading to more undifferentiated cells. Crystal violet staining and cell cycle analysis revealed that silencing of mHotair promoted the proliferation of iMAD cells regardless of BMP9 induction. Moreover, ectopic bone masses developed from mHotair-knockdown iMAD cells exhibited higher expression of PCNA than the control group. Taken together, our results demonstrated that murine mHotair is an important regulator of BMP9-induced MSC osteogenesis by targeting cell cycle and proliferation.
Journal	Aging
Volume Number	13
PubMed Central reference number	PMC7906180
Issue Number	3
PubMed reference number	33461171
e-ISSN	19454589
DOI	10.18632/aging.202384
Language	English
Publisher	Impact Journals
Publisher Date	2021-01-10
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2021 Li et al.
Subject Keyword	long non-coding RNA HOTAIR BMP9 osteogenic differentiation mesenchymal stem cell
Content Type	Text
Resource Type	Article
Subject	Aging Cell Biology