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Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342
Insulin promotes bone formation via a well-studied canonical signaling pathway. An adapter in this pathway, insulin-receptor substrate (IRS)-1, has been implicated in the diabetic osteopathy provoked by impaired insulin signaling. To further investigate IRS-1’s role in the bone metabolism, we genera...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102111/ https://www.ncbi.nlm.nih.gov/pubmed/27623927 http://dx.doi.org/10.1096/fj.201600445RR |
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author | Guo, Yue Tang, Chen-Yi Man, Xiao-Fei Tang, Hao-Neng Tang, Jun Wang, Fang Zhou, Ci-La Tan, Shu-Wen Feng, Yun-Zhi Zhou, Hou-De |
author_facet | Guo, Yue Tang, Chen-Yi Man, Xiao-Fei Tang, Hao-Neng Tang, Jun Wang, Fang Zhou, Ci-La Tan, Shu-Wen Feng, Yun-Zhi Zhou, Hou-De |
author_sort | Guo, Yue |
collection | PubMed |
description | Insulin promotes bone formation via a well-studied canonical signaling pathway. An adapter in this pathway, insulin-receptor substrate (IRS)-1, has been implicated in the diabetic osteopathy provoked by impaired insulin signaling. To further investigate IRS-1’s role in the bone metabolism, we generated Irs-1-deficient Irs-1(smla/smla) mice. These null mice developed a spontaneous mutation that led to an increase in trabecular thickness (Tb.Th) in 12-mo-old, but not in 2-mo-old mice. Analyses of the bone marrow stromal cells (BMSCs) from these mice revealed their differential expression of osteogenesis-related genes and miRNAs. The expression of miR-342, predicted and then proven to target the gene encoding collagen type Iα2 (COL1A2), was reduced in BMSCs derived from Irs-1-null mice. COL1A2 expression was then shown to be age dependent in osteoblasts and BMSCs derived from Irs-1(smla/smla) mice. After the induction of osteogenesis in BMSCs, miR-342 expression correlated inversely with that of Col1a2. Further, Col1a2-specific small interfering RNA (siRNA) reduced alkaline phosphatase (ALP) activity and inhibited BMSC differentiation into osteocyte-like cells, both in wild-type (WT) and Irs-1(smla/smla) mice. Conversely, in Irs-1(smla/smla) osteocytes overexpressing COL1A2, ALP-positive staining was stronger than in WT osteocytes. In summary, we uncovered a temporal regulation of BMSC differentiation/bone formation, controlled via Irs-1/miR-342 mediated regulation of Col1a2 expression.—Guo, Y., Tang, C.-Y., Man, X.-F., Tang, H.-N., Tang, J., Wang, F., Zhou, C.-L., Tan, S.-W., Feng, Y.-Z., Zhou, H.-D. Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342. |
format | Online Article Text |
id | pubmed-5102111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-51021112016-11-10 Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 Guo, Yue Tang, Chen-Yi Man, Xiao-Fei Tang, Hao-Neng Tang, Jun Wang, Fang Zhou, Ci-La Tan, Shu-Wen Feng, Yun-Zhi Zhou, Hou-De FASEB J Research Insulin promotes bone formation via a well-studied canonical signaling pathway. An adapter in this pathway, insulin-receptor substrate (IRS)-1, has been implicated in the diabetic osteopathy provoked by impaired insulin signaling. To further investigate IRS-1’s role in the bone metabolism, we generated Irs-1-deficient Irs-1(smla/smla) mice. These null mice developed a spontaneous mutation that led to an increase in trabecular thickness (Tb.Th) in 12-mo-old, but not in 2-mo-old mice. Analyses of the bone marrow stromal cells (BMSCs) from these mice revealed their differential expression of osteogenesis-related genes and miRNAs. The expression of miR-342, predicted and then proven to target the gene encoding collagen type Iα2 (COL1A2), was reduced in BMSCs derived from Irs-1-null mice. COL1A2 expression was then shown to be age dependent in osteoblasts and BMSCs derived from Irs-1(smla/smla) mice. After the induction of osteogenesis in BMSCs, miR-342 expression correlated inversely with that of Col1a2. Further, Col1a2-specific small interfering RNA (siRNA) reduced alkaline phosphatase (ALP) activity and inhibited BMSC differentiation into osteocyte-like cells, both in wild-type (WT) and Irs-1(smla/smla) mice. Conversely, in Irs-1(smla/smla) osteocytes overexpressing COL1A2, ALP-positive staining was stronger than in WT osteocytes. In summary, we uncovered a temporal regulation of BMSC differentiation/bone formation, controlled via Irs-1/miR-342 mediated regulation of Col1a2 expression.—Guo, Y., Tang, C.-Y., Man, X.-F., Tang, H.-N., Tang, J., Wang, F., Zhou, C.-L., Tan, S.-W., Feng, Y.-Z., Zhou, H.-D. Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342. Federation of American Societies for Experimental Biology 2016-12 2016-09-13 /pmc/articles/PMC5102111/ /pubmed/27623927 http://dx.doi.org/10.1096/fj.201600445RR Text en © The Author(s) http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) (http://creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Guo, Yue Tang, Chen-Yi Man, Xiao-Fei Tang, Hao-Neng Tang, Jun Wang, Fang Zhou, Ci-La Tan, Shu-Wen Feng, Yun-Zhi Zhou, Hou-De Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 |
title | Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 |
title_full | Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 |
title_fullStr | Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 |
title_full_unstemmed | Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 |
title_short | Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342 |
title_sort | insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen iα2 expression via mir-342 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102111/ https://www.ncbi.nlm.nih.gov/pubmed/27623927 http://dx.doi.org/10.1096/fj.201600445RR |
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