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Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss

Previous studies indicated that let-7 enhances osteogenesis and bone formation of human adipose-derived mesenchymal stem cells (MSCs). We also have confirmed that let-7f-5p expression was upregulated during osteoblast differentiation in rat bone marrow-derived MSCs (BMSCs) and was downregulated in t...

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Autores principales: Shen, Geng-Yang, Ren, Hui, Shang, Qi, Zhao, Wen-Hua, Zhang, Zhi-Da, Yu, Xiang, Huang, Jin-Jing, Tang, Jing-Jing, Yang, Zhi-Dong, Liang, De, Jiang, Xiao-Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775285/
https://www.ncbi.nlm.nih.gov/pubmed/31592234
http://dx.doi.org/10.7150/ijbs.33490
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author Shen, Geng-Yang
Ren, Hui
Shang, Qi
Zhao, Wen-Hua
Zhang, Zhi-Da
Yu, Xiang
Huang, Jin-Jing
Tang, Jing-Jing
Yang, Zhi-Dong
Liang, De
Jiang, Xiao-Bing
author_facet Shen, Geng-Yang
Ren, Hui
Shang, Qi
Zhao, Wen-Hua
Zhang, Zhi-Da
Yu, Xiang
Huang, Jin-Jing
Tang, Jing-Jing
Yang, Zhi-Dong
Liang, De
Jiang, Xiao-Bing
author_sort Shen, Geng-Yang
collection PubMed
description Previous studies indicated that let-7 enhances osteogenesis and bone formation of human adipose-derived mesenchymal stem cells (MSCs). We also have confirmed that let-7f-5p expression was upregulated during osteoblast differentiation in rat bone marrow-derived MSCs (BMSCs) and was downregulated in the vertebrae of patients with glucocorticoid (GC)-induced osteoporosis (GIOP). The study was performed to determine the role of let-7f-5p in GC-inhibited osteogenic differentiation of murine BMSCs in vitro and in GIOP in vivo. Here, we report that dexamethasone (Dex) inhibited osteogenic differentiation of BMSCs and let-7f-5p expression, while increasing the expression of transforming growth factor beta receptor 1 (TGFBR1), a direct target of let-7f-5p during osteoblast differentiation under Dex conditions. In addition, let-7f-5p promoted osteogenic differentiation of BMSCs, as indicated by the promotion of alkaline phosphatase (ALP) staining and activity, Von Kossa staining, and osteogenic marker expression (Runx2,Osx, Alp, and Ocn), but decreased TGFBR1 expression in the presence of Dex. However, overexpression of TGFBR1 reversed the upregulation of let-7f-5p during Dex-treated osteoblast differentiation. Knockdown of TGFBR1 reversed the effect of let-7f-5p downregulation during Dex-treated osteogenic differentiation of BMSCs. We also found that glucocorticoid receptor (GR) mediated transcriptional silencing of let-7f-5p and its knockdown enhanced Dex-inhibited osteogenic differentiation. Further, when injected in vivo, agomiR-let-7f-5p significantly reversed bone loss induced by Dex, as well as increased osteogenic marker expression (Runx2, Osx, Alp, and Ocn) and decreased TGFBR1 expression in bone extracts. These findings indicated that the regulatory axis of GR/let-7f-5p/TGFBR1 may be important for Dex-inhibited osteoblast differentiation and that let-7f-5p may be a useful therapeutic target for GIOP.
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spelling pubmed-67752852019-10-07 Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss Shen, Geng-Yang Ren, Hui Shang, Qi Zhao, Wen-Hua Zhang, Zhi-Da Yu, Xiang Huang, Jin-Jing Tang, Jing-Jing Yang, Zhi-Dong Liang, De Jiang, Xiao-Bing Int J Biol Sci Research Paper Previous studies indicated that let-7 enhances osteogenesis and bone formation of human adipose-derived mesenchymal stem cells (MSCs). We also have confirmed that let-7f-5p expression was upregulated during osteoblast differentiation in rat bone marrow-derived MSCs (BMSCs) and was downregulated in the vertebrae of patients with glucocorticoid (GC)-induced osteoporosis (GIOP). The study was performed to determine the role of let-7f-5p in GC-inhibited osteogenic differentiation of murine BMSCs in vitro and in GIOP in vivo. Here, we report that dexamethasone (Dex) inhibited osteogenic differentiation of BMSCs and let-7f-5p expression, while increasing the expression of transforming growth factor beta receptor 1 (TGFBR1), a direct target of let-7f-5p during osteoblast differentiation under Dex conditions. In addition, let-7f-5p promoted osteogenic differentiation of BMSCs, as indicated by the promotion of alkaline phosphatase (ALP) staining and activity, Von Kossa staining, and osteogenic marker expression (Runx2,Osx, Alp, and Ocn), but decreased TGFBR1 expression in the presence of Dex. However, overexpression of TGFBR1 reversed the upregulation of let-7f-5p during Dex-treated osteoblast differentiation. Knockdown of TGFBR1 reversed the effect of let-7f-5p downregulation during Dex-treated osteogenic differentiation of BMSCs. We also found that glucocorticoid receptor (GR) mediated transcriptional silencing of let-7f-5p and its knockdown enhanced Dex-inhibited osteogenic differentiation. Further, when injected in vivo, agomiR-let-7f-5p significantly reversed bone loss induced by Dex, as well as increased osteogenic marker expression (Runx2, Osx, Alp, and Ocn) and decreased TGFBR1 expression in bone extracts. These findings indicated that the regulatory axis of GR/let-7f-5p/TGFBR1 may be important for Dex-inhibited osteoblast differentiation and that let-7f-5p may be a useful therapeutic target for GIOP. Ivyspring International Publisher 2019-08-19 /pmc/articles/PMC6775285/ /pubmed/31592234 http://dx.doi.org/10.7150/ijbs.33490 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Shen, Geng-Yang
Ren, Hui
Shang, Qi
Zhao, Wen-Hua
Zhang, Zhi-Da
Yu, Xiang
Huang, Jin-Jing
Tang, Jing-Jing
Yang, Zhi-Dong
Liang, De
Jiang, Xiao-Bing
Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
title Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
title_full Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
title_fullStr Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
title_full_unstemmed Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
title_short Let-7f-5p regulates TGFBR1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
title_sort let-7f-5p regulates tgfbr1 in glucocorticoid-inhibited osteoblast differentiation and ameliorates glucocorticoid-induced bone loss
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775285/
https://www.ncbi.nlm.nih.gov/pubmed/31592234
http://dx.doi.org/10.7150/ijbs.33490
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