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Mol Ther. 2019 Feb 6;27(2):394-410. doi: 10.1016/j.ymthe.2018.11.019. Epub 2018 Dec 7.

The Long Non-coding RNA-ORLNC1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Fate.

Author information

1
Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China. Electronic address: yangray83@vip.qq.com.
2
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
3
Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
4
Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
5
Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China.
6
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; Central Laboratory of Scientific Research, Bashkir State Medical University, Ufa 450008, Russia.
7
Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China. Electronic address: caibz@ems.hrbmu.edu.cn.
8
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, China. Electronic address: yflora915@163.com.

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and the shift between osteogenic and adipogenic differentiation determines bone mass. The aim of this study was to identify whether lncRNAs are involved in the differentiation commitment of BMSCs during osteoporosis. Here, we found ORLNC1, a functionally undefined lncRNA that is highly conserved, which exhibited markedly higher expression levels in BMSCs, bone tissue, and the serum of OVX-induced osteoporotic mice than sham-operated counterparts. Notably, a similar higher abundance of lncRNA-ORLNC1 expression was also observed in the bone tissue of osteoporotic patients. The transgenic mice overexpressing lncRNA-ORLNC1 showed a substantial increase in the osteoporosis-associated bone loss and decline in the osteogenesis of BMSCs. The BMSCs pretreated with lncRNA-ORLNC1-overexpressing lentivirus vector exhibited the suppressed capacity of osteogenic differentiation and oppositely enhanced adipogenic differentiation. We then established that lncRNA-ORLNC1 acted as a competitive endogenous RNA (ceRNA) for miR-296. Moreover, miR-296 was found markedly upregulated during osteoblast differentiation, and it accelerated osteogenic differentiation by targeting Pten. Taken together, our results indicated that the lncRNA-ORLNC1-miR-296-Pten axis may be a critical regulator of the osteoporosis-related switch between osteogenesis and adipogenesis of BMSCs and might represent a plausible therapeutic target for improving osteoporotic bone loss.

KEYWORDS:

BMSCs; Pten; adipogenic differentiation; bone formation; lncRNA; miR-296; osteogenic differentiation; osteoporosis

PMID:
30638773
PMCID:
PMC6369452
[Available on 2020-02-06]
DOI:
10.1016/j.ymthe.2018.11.019

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