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

Journal Article · Sat Nov 01 04:00:00 EDT 2008 · Experimental Cell Research

OSTI ID:21176137

Weijun, Luo ^[1]; Shitaye, Hailu; Friedman, Michael ^[2]; Bennett, Christina N ^[3]; Miller, Joshua ^[4]; MacDougald, Ormond A ^[3]

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1. Department of Biomedical Engineering, Medical School, University of Michigan (United States)
2. Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 311 Hill Pavilion Philadelphia, PA 19104 (United States)
3. Department of Physiology and Biophysics, Medical School, University of Michigan (United States)
4. Department of Orthopedic Surgery, Medical School, University of Michigan (United States)

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 {mu}g/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.

• OSTI ID: 21176137
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 18 Vol. 314; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
CELL DIFFERENTIATION
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DEXTRAN
HEPARIN
IN VITRO
IN VIVO
INDUCTION
LIPIDS
MORPHOLOGY
PHOSPHORYLATION
SKELETON
STEM CELLS
SULFATES
TIME DEPENDENCE