OSTEOPOROSIS / RESEARCH PAPER
MALAT1/miR-320a in BMSC function may inform on mechanisms underlying osteoporosis
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1
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University, No. 14, Section 3, South Renmin Road, Chengdu, 610041, China
2
Department of Orthodontics,Yantai Stromatological Hospital, Yantai,Shangdong Province,People’s Republic of China, No.142,North Great
CORRESPONDING AUTHOR
Yunfeng Li   

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University, No. 14, Section 3, South Renmin Road, Chengdu, 610041, China
Submission date: 2018-07-25
Final revision date: 2019-02-11
Acceptance date: 2019-03-19
Online publication date: 2021-03-21
 
Arch Med Sci 2022;18(6)
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
growing evidence supports the involvement of long noncoding RNAs (lncRNAs) in bone metabolism and diseases. This study aims to investigate the involvement of the lncRNA MALAT1 in the pathological process of osteoporosis and the effects of MALAT1 on the regulation of BMSC differentiation through competitive endogenous RNA (ceRNA) mechanisms.

Material and methods:
the expression of MALAT1 and miR-320a was determined using RT-PCR in bone tissue derived from female SD(Sprague Dawley) rats with osteoporosis. Immumohistochemical staining (IHC) was used to evaluate the expression of neuropilin-1 (NRP-1) and β-catenin. BMSCs were divided into 4 groups: Control, NC (Negative control), MALAT1 siRNA, and miR-320a mimics. Fourty-eight hours later, the effect of MALAT1 on the miR-320a expression, proliferation and osteogenic differentiation of BMSCs was investigated. Two weeks later, the cell activity, alkaline phosphatase (ALP) activity, and mRNA expression of Osterix and Runx2 were evaluated. Three weeks later, alizarin red staining of calcified nodules and Western blot analysis of the expression of β-catenin, NRP-1, osteocalcin (OCN), osteopontin (OPN) were performed.

Results:
downregulated MALAT1 or upregulated miR-320a expression inhibited the activity and osteogenic differentiation of BMSCs, resulting in low ALP activity and NRP-1 expression, fewer calcified nodules, decreased mRNA levels of Osterix and Runx2, and inhibited expression of NRP-1, OCN, and OPN. MALAT1 silencing did not decrease the protein level of β-catenin in the cytoplasm but suppressed that in the nucleus.

Conclusions:
downregulated MALAT1 and upregulated miR-320a expression play an important role in the pathological process of osteoporosis, via inhibition of the osteogenic differentiation of BMSCs.

eISSN:1896-9151
ISSN:1734-1922