Heparin affects human bone marrow stromal cell fate: Promoting osteogenic and reducing adipogenic differentiation and conversion
| Autor: | Franz Jakob, Tatjana Schilling, Julia Dotterweich, Verena Schneider, Norbert Schütze, Solange Le Blanc, Viola Zehe, Meike Simann, Melanie Krug |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Genetic Markers Male Histology Stromal cell Physiology Endocrinology Diabetes and Metabolism Bone Marrow Cells Bone Morphogenetic Protein 4 Bone morphogenetic protein Fibroblast growth factor Osteocytes Bone resorption Osteogenesis medicine Adipocytes Humans Cell Lineage Osteopontin RNA Messenger Adaptor Proteins Signal Transducing Aged Adipogenesis biology Heparin Anticoagulants Cell Differentiation Mesenchymal Stem Cells Middle Aged Lipids Recombinant Proteins RUNX2 Wnt Proteins Bone Morphogenetic Proteins biology.protein Cancer research Intercellular Signaling Peptides and Proteins Osteoporosis Female medicine.drug Signal Transduction |
| Zdroj: | Bone. 78 |
| ISSN: | 1873-2763 |
| Popis: | Heparins are broadly used for the prevention and treatment of thrombosis and embolism. Yet, osteoporosis is considered to be a severe side effect in up to one third of all patients on long-term treatment. However, the mechanisms underlying this clinical problem are only partially understood. To investigate if heparin affects differentiation of skeletal precursors, we examined the effects of heparin on the osteogenic and adipogenic lineage commitment and differentiation of primary human bone marrow stromal cells (hBMSCs). Due to the known inverse relationship between adipogenesis and osteogenesis and the capacity of pre-differentiated cells to convert into the respective other lineage, we also determined heparin effects on osteogenic conversion and adipogenic differentiation/conversion. Interestingly, heparin did not only significantly increase mRNA expression and enzyme activity of the osteogenic marker alkaline phosphatase (ALP), but it also promoted mineralization during osteogenic differentiation and conversion. Furthermore, the mRNA expression of the osteogenic marker bone morphogenic protein 4 (BMP4) was enhanced. In addition, heparin administration partly prevented adipogenic differentiation and conversion demonstrated by reduced lipid droplet formation along with a decreased expression of adipogenic markers. Moreover, luciferase reporter assays, inhibitor experiments and gene expression analyses revealed that heparin had putative permissive effects on osteogenic signaling via the BMP pathway and reduced the mRNA expression of the Wnt pathway inhibitors dickkopf 1 (DKK1) and sclerostin (SOST). Taken together, our data show a rather supportive than inhibitory effect of heparin on osteogenic hBMSC differentiation and conversion in vitro. Further studies will have to investigate the net effects of heparin administration on bone formation versus bone resorption in vivo to unravel the molecular mechanisms of heparin-associated osteoporosis and reconcile conflicting experimental data with clinical observations. |
| Databáze: | OpenAIRE |
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