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Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance

Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound synd...

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Autores principales: Yu, Chieh, Peall, Ian W., Pham, Son H., Okolicsanyi, Rachel K., Griffiths, Lyn R., Haupt, Larisa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312587/
https://www.ncbi.nlm.nih.gov/pubmed/32485953
http://dx.doi.org/10.3390/ijms21113884
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author Yu, Chieh
Peall, Ian W.
Pham, Son H.
Okolicsanyi, Rachel K.
Griffiths, Lyn R.
Haupt, Larisa M.
author_facet Yu, Chieh
Peall, Ian W.
Pham, Son H.
Okolicsanyi, Rachel K.
Griffiths, Lyn R.
Haupt, Larisa M.
author_sort Yu, Chieh
collection PubMed
description Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound syndecans (SDCs) and glypicans (GPCs) mediate hMSC lineage differentiation and with syndecan-1 (SDC-1) reported in both adipogenesis and osteogenesis, these macromolecules are potential regulators of the osteo-adipogenic balance. Here, we disrupted the HSPG profile in primary hMSC cultures via temporal knockdown (KD) of SDC-1 using RNA interference (RNAi) in undifferentiated, osteogenic and adipogenic differentiated hMSCs. SDC-1 KD cultures were examined for osteogenic and adipogenic lineage markers along with changes in HSPG profile and common signalling pathways implicated in hMSC lineage fate. Undifferentiated hMSC SDC-1 KD cultures exhibited a pro-adipogenic phenotype with subsequent osteogenic differentiation demonstrating enhanced maturation of osteoblasts. In cultures where SDC-1 KD was performed following initiation of differentiation, increased adipogenic gene and protein marker expression along with increased Oil Red O staining identified enhanced adipogenesis, with impaired osteogenesis also observed in these cultures. These findings implicate SDC-1 as a facilitator of the hMSC osteo-adipogenic balance during early induction of lineage differentiation.
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spelling pubmed-73125872020-06-29 Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance Yu, Chieh Peall, Ian W. Pham, Son H. Okolicsanyi, Rachel K. Griffiths, Lyn R. Haupt, Larisa M. Int J Mol Sci Article Bone marrow-derived human mesenchymal stems cells (hMSCs) are precursors to adipocyte and osteoblast lineage cells. Dysregulation of the osteo-adipogenic balance has been implicated in pathological conditions involving bone loss. Heparan sulfate proteoglycans (HSPGs) such as cell membrane-bound syndecans (SDCs) and glypicans (GPCs) mediate hMSC lineage differentiation and with syndecan-1 (SDC-1) reported in both adipogenesis and osteogenesis, these macromolecules are potential regulators of the osteo-adipogenic balance. Here, we disrupted the HSPG profile in primary hMSC cultures via temporal knockdown (KD) of SDC-1 using RNA interference (RNAi) in undifferentiated, osteogenic and adipogenic differentiated hMSCs. SDC-1 KD cultures were examined for osteogenic and adipogenic lineage markers along with changes in HSPG profile and common signalling pathways implicated in hMSC lineage fate. Undifferentiated hMSC SDC-1 KD cultures exhibited a pro-adipogenic phenotype with subsequent osteogenic differentiation demonstrating enhanced maturation of osteoblasts. In cultures where SDC-1 KD was performed following initiation of differentiation, increased adipogenic gene and protein marker expression along with increased Oil Red O staining identified enhanced adipogenesis, with impaired osteogenesis also observed in these cultures. These findings implicate SDC-1 as a facilitator of the hMSC osteo-adipogenic balance during early induction of lineage differentiation. MDPI 2020-05-29 /pmc/articles/PMC7312587/ /pubmed/32485953 http://dx.doi.org/10.3390/ijms21113884 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Chieh
Peall, Ian W.
Pham, Son H.
Okolicsanyi, Rachel K.
Griffiths, Lyn R.
Haupt, Larisa M.
Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance
title Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance
title_full Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance
title_fullStr Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance
title_full_unstemmed Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance
title_short Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance
title_sort syndecan-1 facilitates the human mesenchymal stem cell osteo-adipogenic balance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312587/
https://www.ncbi.nlm.nih.gov/pubmed/32485953
http://dx.doi.org/10.3390/ijms21113884
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