Cargando…

lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway

Background: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MS...

Descripción completa

Detalles Bibliográficos
Autores principales: Yin, Xin-Hua, Wang, Xiao-Yuan, Liu, Shi-Chang, Yan, Liang, He, Bao-Rong, Hao, Ding-Jun, Yang, Ming, Liu, Zhong-Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699766/
https://www.ncbi.nlm.nih.gov/pubmed/36375472
http://dx.doi.org/10.18632/aging.204381
_version_ 1784839155151273984
author Yin, Xin-Hua
Wang, Xiao-Yuan
Liu, Shi-Chang
Yan, Liang
He, Bao-Rong
Hao, Ding-Jun
Yang, Ming
Liu, Zhong-Kai
author_facet Yin, Xin-Hua
Wang, Xiao-Yuan
Liu, Shi-Chang
Yan, Liang
He, Bao-Rong
Hao, Ding-Jun
Yang, Ming
Liu, Zhong-Kai
author_sort Yin, Xin-Hua
collection PubMed
description Background: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MSCs. We focused on Hedgehog interacting protein (HHIP), because HHIP mRNA and lncRNA HHIP-AS1 were gradually down-regulated on days 0, 7, and 14 during osteogenic differentiation. In addition, the gene coding lncRNA HHIP-AS1 is located on the anti-sense of Hhip gene, implying the potential interaction between lncRNA HHIP-AS1 and HHIP mRNA. Methods: BM-MSCs with over-expressed or silenced lncRNA HHIP-AS1 were constructed to explore the biological role of HHIP-AS1 in osteogenic differentiation. BM-MSCs were lysed to determine the alkaline phosphatase activity. Fluorescence in situ hybridization and immunofluorescence were performed to analyze HHIP-AS1, HHIP, RUNX2 and osteocalcin. Results: Overexpression of lncRNA HHIP-AS1 increased HHIP expression, which suppressed Hedgehog signaling pathway, as indicated by the reduction of SMO, Gli1 and Gli2. The suppression of Hedgehog signal was associated with the inhibited osteogenesis. HHIP knockdown abolished the suppression of osteogenesis induced by lncRNA HHIP-AS1 overexpression. Through binding to HHIP mRNA, lncRNA HHIP-AS1 recruited ELAVL1 to HHIP mRNA, whereby increasing the mRNA stability and the protein level. Conclusions: This study revealed that down-regulation of HHIP due to lncRNA HHIP-AS1 reduction promoted the osteogenic differentiation of BM-MSCs though removing the suppression of Hedgehog signal.
format Online
Article
Text
id pubmed-9699766
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Impact Journals
record_format MEDLINE/PubMed
spelling pubmed-96997662022-11-28 lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway Yin, Xin-Hua Wang, Xiao-Yuan Liu, Shi-Chang Yan, Liang He, Bao-Rong Hao, Ding-Jun Yang, Ming Liu, Zhong-Kai Aging (Albany NY) Research Paper Background: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MSCs. We focused on Hedgehog interacting protein (HHIP), because HHIP mRNA and lncRNA HHIP-AS1 were gradually down-regulated on days 0, 7, and 14 during osteogenic differentiation. In addition, the gene coding lncRNA HHIP-AS1 is located on the anti-sense of Hhip gene, implying the potential interaction between lncRNA HHIP-AS1 and HHIP mRNA. Methods: BM-MSCs with over-expressed or silenced lncRNA HHIP-AS1 were constructed to explore the biological role of HHIP-AS1 in osteogenic differentiation. BM-MSCs were lysed to determine the alkaline phosphatase activity. Fluorescence in situ hybridization and immunofluorescence were performed to analyze HHIP-AS1, HHIP, RUNX2 and osteocalcin. Results: Overexpression of lncRNA HHIP-AS1 increased HHIP expression, which suppressed Hedgehog signaling pathway, as indicated by the reduction of SMO, Gli1 and Gli2. The suppression of Hedgehog signal was associated with the inhibited osteogenesis. HHIP knockdown abolished the suppression of osteogenesis induced by lncRNA HHIP-AS1 overexpression. Through binding to HHIP mRNA, lncRNA HHIP-AS1 recruited ELAVL1 to HHIP mRNA, whereby increasing the mRNA stability and the protein level. Conclusions: This study revealed that down-regulation of HHIP due to lncRNA HHIP-AS1 reduction promoted the osteogenic differentiation of BM-MSCs though removing the suppression of Hedgehog signal. Impact Journals 2022-11-14 /pmc/articles/PMC9699766/ /pubmed/36375472 http://dx.doi.org/10.18632/aging.204381 Text en Copyright: © 2022 Yin et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yin, Xin-Hua
Wang, Xiao-Yuan
Liu, Shi-Chang
Yan, Liang
He, Bao-Rong
Hao, Ding-Jun
Yang, Ming
Liu, Zhong-Kai
lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway
title lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway
title_full lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway
title_fullStr lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway
title_full_unstemmed lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway
title_short lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway
title_sort lncrna hhip-as1/hhip modulates osteogenic differentiation of bm-mscs by regulating hedgehog signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699766/
https://www.ncbi.nlm.nih.gov/pubmed/36375472
http://dx.doi.org/10.18632/aging.204381
work_keys_str_mv AT yinxinhua lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT wangxiaoyuan lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT liushichang lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT yanliang lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT hebaorong lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT haodingjun lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT yangming lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway
AT liuzhongkai lncrnahhipas1hhipmodulatesosteogenicdifferentiationofbmmscsbyregulatinghedgehogsignalingpathway