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 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.
['Yu|Chieh|C|0000-0003-3712-5491', 'Peall|Ian W|IW|', 'Pham|Son H|SH|', 'Okolicsanyi|Rachel K|RK|', 'Griffiths|Lyn R|LR|0000-0002-6774-5475', 'Haupt|Larisa M|LM|0000-0002-7735-8110']
D017667:Adipocytes D050156:Adipogenesis D050154:Adiposity D002454:Cell Differentiation D019070:Cell Lineage D002462:Cell Membrane D049109:Cell Proliferation D016326:Extracellular Matrix Proteins D019812:Heparan Sulfate Proteoglycans D006801:Humans D059630:Mesenchymal Stem Cells D010006:Osteoblasts D010011:Osteocytes D010012:Osteogenesis D034622:RNA Interference D034741:RNA, Small Interfering D053668:Syndecan-1 D015854:Up-Regulation
syndecan-1 mesenchymal stem cells heparan sulfate proteoglycans adipogenesis osteogenesis lineage fate