PMID- 32485953 OWN - NLM STAT- MEDLINE DCOM- 20210330 LR - 20210330 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 11 DP - 2020 May 29 TI - Syndecan-1 Facilitates the Human Mesenchymal Stem Cell Osteo-Adipogenic Balance. LID - 10.3390/ijms21113884 [doi] LID - 3884 AB - 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. FAU - Yu, Chieh AU - Yu C AUID- ORCID: 0000-0003-3712-5491 AD - Queensland University of Technology, Genomics Research Centre, School of Biomedical Sciences, IHBI, Brisbane, QLD 4059, Australia. FAU - Peall, Ian W AU - Peall IW AD - Queensland University of Technology, Genomics Research Centre, School of Biomedical Sciences, IHBI, Brisbane, QLD 4059, Australia. FAU - Pham, Son H AU - Pham SH AD - Queensland University of Technology, Genomics Research Centre, School of Biomedical Sciences, IHBI, Brisbane, QLD 4059, Australia. FAU - Okolicsanyi, Rachel K AU - Okolicsanyi RK AD - Queensland University of Technology, Genomics Research Centre, School of Biomedical Sciences, IHBI, Brisbane, QLD 4059, Australia. FAU - Griffiths, Lyn R AU - Griffiths LR AUID- ORCID: 0000-0002-6774-5475 AD - Queensland University of Technology, Genomics Research Centre, School of Biomedical Sciences, IHBI, Brisbane, QLD 4059, Australia. FAU - Haupt, Larisa M AU - Haupt LM AUID- ORCID: 0000-0002-7735-8110 AD - Queensland University of Technology, Genomics Research Centre, School of Biomedical Sciences, IHBI, Brisbane, QLD 4059, Australia. LA - eng GR - CY/Australian Postgraduate Award/ GR - Ph.D. Enabling Grant, Haupt/School of Biomedical Sciences, QUT/ PT - Journal Article DEP - 20200529 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Extracellular Matrix Proteins) RN - 0 (Heparan Sulfate Proteoglycans) RN - 0 (RNA, Small Interfering) RN - 0 (SDC1 protein, human) RN - 0 (Syndecan-1) SB - IM MH - Adipocytes/*cytology MH - Adipogenesis MH - Adiposity MH - Cell Differentiation MH - Cell Lineage MH - Cell Membrane/metabolism MH - Cell Proliferation MH - Extracellular Matrix Proteins/metabolism MH - Heparan Sulfate Proteoglycans/chemistry MH - Humans MH - Mesenchymal Stem Cells/*cytology MH - Osteoblasts/cytology MH - Osteocytes/*cytology MH - Osteogenesis MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - Syndecan-1/*metabolism MH - Up-Regulation PMC - PMC7312587 OTO - NOTNLM OT - adipogenesis OT - heparan sulfate proteoglycans OT - lineage fate OT - mesenchymal stem cells OT - osteogenesis OT - syndecan-1 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2020/06/04 06:00 MHDA- 2021/03/31 06:00 PMCR- 2020/06/01 CRDT- 2020/06/04 06:00 PHST- 2020/04/29 00:00 [received] PHST- 2020/05/27 00:00 [revised] PHST- 2020/05/27 00:00 [accepted] PHST- 2020/06/04 06:00 [entrez] PHST- 2020/06/04 06:00 [pubmed] PHST- 2021/03/31 06:00 [medline] PHST- 2020/06/01 00:00 [pmc-release] AID - ijms21113884 [pii] AID - ijms-21-03884 [pii] AID - 10.3390/ijms21113884 [doi] PST - epublish SO - Int J Mol Sci. 2020 May 29;21(11):3884. doi: 10.3390/ijms21113884.