MicroRNA-579-3p promotes the progression of osteoporosis by inhibiting osteogenic differentiation of mesenchymal stem cells through regulating Sirt1
Authors: Z-J Zeng
J Yuan
J-F Yang
B Luo
G-B Qu
Y-H Wang
Y Yuan
P-D Hao
R Yang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: microRNA-579-3P; osteoporosis; osteogenic differentiation; Sirt1; ALP
Affiliations: Department of Orthopedics, The Affiliated Hospital (Traditional Chinese Medicine) of Southwest Medical University, Luzhou, China. .

Abstract:  Objective: To explore whether microRNA-579-3P was involved in the development of osteoporosis, and to investigate the possible molecular mechanisms. Patients and methods: The messenger RNA (mRNA) expression levels of microRNA-579-3P, alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and bone sialoprotein (BSP) in serum samples of osteoporosis patients and normal controls were detected by quantitative Real-time polymerase chain reaction (qRT-PCR), respectively. Meanwhile, the expressions of the above genes during osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) were examined as well. To investigate the effect of microRNA-579-3P on osteogenesis, microRNA-579-3P was overexpressed and knocked down in hMSCs. Subsequently, the mRNA and protein expression levels of osteogenesis-related genes, such as ALP, RUNX2 and BSP, were detected by qRT-PCR and Western blot, respectively. In addition, ALP activity and mineralization forming ability were evaluated by ALP staining and alizarin red staining. Bioinformatics predicted that Sirt1 was the target gene of microRNA-579-3P. Subsequent luciferase reporter gene assay was performed to verify the binding relationship of microRNA-579-3P to Sirt1. Meanwhile, qRT-PCR and Western blot were used to detect the changes in the mRNA and protein expression levels of Sirt1, respectively. After overexpression of microRNA-579-3P and Sirt1, qRT-PCR, Western blot, ALP staining and alizarin red staining assays were performed to detect the osteogenic differentiation of hMSCs. Results: The expression of microRNA-579-3P in serum of patients with osteoporosis was significantly higher than that of normal controls. Meanwhile, the expression of microRNA-579-3P decreased gradually during osteogenic differentiation of hMSCs. Overexpression of microRNA-579-3P significantly reduced the expressions of osteogenic related genes, including ALP, RUNX2 and BSP. Besides, ALP activity and mineralized nodule formation ability decreased obviously as well. Luciferase reporter gene assay showed that microRNA-579-3P could bind to Sirt1. After overexpression of microRNA-579-3P, the mRNA and protein expression levels of Sirt1 were significantly reduced, which were reversed after silence of microRNA-579-3P. Simultaneous overexpression of microRNA-579-3P and Sirt1 could reverse the inhibition of osteogenic differentiation of hMSCs caused by overexpression of microRNA-579-3P alone. Conclusions: MicroRNA-579-3P could inhibit osteogenic differentiation of hMSCs by regulating Sirt1, thereby promoting the development of osteoporosis. 

Retracted: No

PubPeer comments:
 This paper appears to belong to a set of (as of today) seven papers that all show very similar, and sometimes overlapping, panels with Alizarin Red-stained cells. These papers were published by different authors at different hospitals, suggesting the photos all might have originated from the same source. The papers are: * AG Gao et al., , The First Affiliated Hospital Of Soochow University, Suzhou, DOI: 10.26355 eurrev_201807_15527- https: pubpeer.com publications 65A5976CDD42166D927AF2D3BA0B56 * B Luo et al., The Affiliated Hospital (Traditional Chinese Medicine) of Southwest Medical University, Luzhou, DOI: 10.26355 eurrev_201908_18717 - https: pubpeer.com publications 20DFC925FC185C52D8BA99B153F510 * Changgong Lan et al., The First Affiliated Hospital of Jinan University, Guangzhou, DOI: 10.3892 etm.2019.8246 - https: pubpeer.com publications 1D79EA9F787AF36661079482544D12 * FB Weng et al., The Ninth Peopleu2019s Hospital of Suzhou, Suzhou, DOI: 10.26355 eurrev_201912_19759 - https: pubpeer.com publications D63F002727B3A990A4571F7D4B6F56 * GC Gao et al., The Second Affiliated Hospital of Nanchang University, Nanchang, DOI: 10.26355 eurrev_202001_20029 - https: pubpeer.com publications F04C25EBF6963C260938DF3B6BB999 * JY Li et al., Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, DOI: 10.26355 eurrev_201908_18519 - https: pubpeer.com publications 6171C86828BF72676BB2B178610093 * YC Fu et al., Health Management Center, Weifang Peopleu2019s Hospital, Weifang, DOI: 10.26355 eurrev_201908_18632 - https: pubpeer.com publications FF66C46D23036BC26668481C279E4B Here is a collage of the images from these papers. Boxes of the same color highlight panels or parts of panels that look similar. ![file] ,