Disruption of cell-matrix interactions by heparin enhances mesenchymal progenitor adipocyte differentiation.

TitleDisruption of cell-matrix interactions by heparin enhances mesenchymal progenitor adipocyte differentiation.
Publication TypeJournal Article
Year of Publication2008
AuthorsLuo W, Shitaye H, Friedman MS, Bennett CN, Miller J, Macdougald OA, Hankenson KD
JournalExp Cell Res
Volume314
Issue18
Pagination3382-91
Date Published2008 Nov 01
ISSN1090-2422
KeywordsAdipocytes, Animals, Base Sequence, Blotting, Western, Cell Adhesion, Cell Differentiation, Cells, Cultured, Dextran Sulfate, Dose-Response Relationship, Drug, Extracellular Matrix, Heparin, Mesenchymal Stromal Cells, Mice, Molecular Sequence Data, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction
Abstract

<p>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.</p>

DOI10.1016/j.yexcr.2008.07.003
Alternate JournalExp. Cell Res.
PubMed ID18674534
PubMed Central IDPMC3179914
Grant ListR01 AR049682 / AR / NIAMS NIH HHS / United States
AR049682 / AR / NIAMS NIH HHS / United States
DE017471 / DE / NIDCR NIH HHS / United States
R01 AR054714 / AR / NIAMS NIH HHS / United States
R01 DE017471 / DE / NIDCR NIH HHS / United States
R01 AR054714-05 / AR / NIAMS NIH HHS / United States