lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway

Abstract Background We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. Methods The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The target...

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Autores principales:	Xiao Yu, Peng-Ze Rong, Meng-Sheng Song, Ze-Wen Shi, Gong Feng, Xian-Jun Chen, Lin Shi, Cheng-Hao Wang, Qing-Jiang Pang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	LncRNA SNHG1 miR-181c-5p SFRP1 Wnt signal Bone remodeling Angiogenesis Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/41d82b8609d34da2aff36a8120d1444e
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spelling	oai:doaj.org-article:41d82b8609d34da2aff36a8120d1444e2021-11-07T12:19:08ZlncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway10.1186/s10020-021-00392-21076-15511528-3658https://doaj.org/article/41d82b8609d34da2aff36a8120d1444e2021-11-01T00:00:00Zhttps://doi.org/10.1186/s10020-021-00392-2https://doaj.org/toc/1076-1551https://doaj.org/toc/1528-3658Abstract Background We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. Methods The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of β-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. Results SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/β-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. Conclusions Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/β-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis. Graphic abstractXiao YuPeng-Ze RongMeng-Sheng SongZe-Wen ShiGong FengXian-Jun ChenLin ShiCheng-Hao WangQing-Jiang PangBMCarticleLncRNA SNHG1miR-181c-5pSFRP1Wnt signalBone remodelingAngiogenesisTherapeutics. PharmacologyRM1-950BiochemistryQD415-436ENMolecular Medicine, Vol 27, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	LncRNA SNHG1 miR-181c-5p SFRP1 Wnt signal Bone remodeling Angiogenesis Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
spellingShingle	LncRNA SNHG1 miR-181c-5p SFRP1 Wnt signal Bone remodeling Angiogenesis Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436 Xiao Yu Peng-Ze Rong Meng-Sheng Song Ze-Wen Shi Gong Feng Xian-Jun Chen Lin Shi Cheng-Hao Wang Qing-Jiang Pang lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway
description	Abstract Background We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. Methods The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of β-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. Results SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/β-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. Conclusions Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/β-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis. Graphic abstract
format	article
author	Xiao Yu Peng-Ze Rong Meng-Sheng Song Ze-Wen Shi Gong Feng Xian-Jun Chen Lin Shi Cheng-Hao Wang Qing-Jiang Pang
author_facet	Xiao Yu Peng-Ze Rong Meng-Sheng Song Ze-Wen Shi Gong Feng Xian-Jun Chen Lin Shi Cheng-Hao Wang Qing-Jiang Pang
author_sort	Xiao Yu
title	lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway
title_short	lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway
title_full	lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway
title_fullStr	lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway
title_full_unstemmed	lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway
title_sort	lncrna snhg1 induced by sp1 regulates bone remodeling and angiogenesis via sponging mir-181c-5p and modulating sfrp1/wnt signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/41d82b8609d34da2aff36a8120d1444e
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lncRNA SNHG1 induced by SP1 regulates bone remodeling and angiogenesis via sponging miR-181c-5p and modulating SFRP1/Wnt signaling pathway

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