Disruption of cell–matrix interactions by heparin enhances mesenchymal progenitor adipocyte differentiation
| Autor: | Christina N. Bennett, Michael Friedman, Weijun Luo, Ormond A. MacDougald, Kurt D. Hankenson, Joshua W. Miller, Hailu Shitaye |
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| Rok vydání: | 2008 |
| Předmět: |
Cellular differentiation
Blotting Western Molecular Sequence Data Biology Article Focal adhesion Mice Adipocytes Cell Adhesion medicine Animals Progenitor cell Cell adhesion Cells Cultured Base Sequence Dose-Response Relationship Drug Heparin Reverse Transcriptase Polymerase Chain Reaction Dextran Sulfate Cell Differentiation Mesenchymal Stem Cells Osteoblast Cell Biology Extracellular Matrix Cell biology Fibronectin medicine.anatomical_structure Biochemistry Adipogenesis biology.protein Signal Transduction medicine.drug |
| Zdroj: | Experimental Cell Research. 314:3382-3391 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2008.07.003 |
| Popis: | Differentiation of marrow-derived mesenchymal progenitors to either the osteoblast or adipocyte lineage is reciprocally regulated. Factors that promote osteoblastogenesis inhibit adipogenesis, while adipogenic factors are inhibitory to osteoblast differentiation. Heparin, a soluble glycosaminoglycan, inhibits bone formation in vivo and osteoblast cell differentiation and function in vitro, and has been shown to promote adipocyte differentiation. To elucidate the role that heparin plays in the adipogenic induction of murine mesenchymal progenitors, we studied immortalized marrow stromal cells (IM-MSC), the MSC cell line, ST2, and 3T3L1 pre-adipocytes. Heparin alone was not sufficient to induce adipogenesis, but enhanced the induction under a variety of adipogenic cocktails. This effect was both dose- and time-dependent. Heparin showed a positive effect at concentrations > 0.1 microg/ml when applied before day 3 during the induction course. Heparin's effect on adipogenesis was independent of cell proliferation, cell density, and extracellular lipid. This effect is likely related to the unique structure of heparin because another polyanionic glycosaminoglycan, dextran sulfate, did not promote adipogenic differentiation. Heparin treatment altered morphology and adhesion characteristics of progenitor cells, resulting in cell rounding and aggregation. As well, heparin counteracted the known inhibitory effect of fibronectin on adipogenesis and decreased basal focal adhesion kinase and paxillin phosphorylation. We conclude that heparin-mediated disruption of cell-matrix adhesion enhances adipogenic potential. |
| Databáze: | OpenAIRE |
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