The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate

J. Christopher Fritton, Yuki Kawashima, Wilson Mejia, Hayden Williams Courtland, Sebastien Elis, Hui Sun, Yinjgie Wu, Clifford J. Rosen, David Clemmons, Shoshana Yakar

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11 Scopus citations

Abstract

Age-related osteoporosis is accompanied by an increase in marrow adiposity and a reduction in serum insulin-like growth factor-1 (IGF-1) and the binding proteins that stabilize IGF-1. To determine the relationship between these proteins and bone marrow adiposity, we evaluated the adipogenic potential of marrow-derived mesenchymal stromal cells (MSCs) from mice with decreased serum IGF-1 due to knockdown of IGF-1 production by the liver or knock-out of the binding proteins. We employed 10-16-week-old, liver-specific IGF-1-deficient, IGFBP-3 knockout (BP3KO) and acid-labile subunit knock-out (ALSKO) mice. We found that expression of the late adipocyte differentiation marker peroxisome proliferator-activated receptor γ was increased in marrow isolated from ALSKO mice. When induced with adipogenic media, MSC cultures from ALSKO mice revealed a significantly greater number of differentiated adipocytes compared with controls. MSCs from ALSKO mice also exhibited decreased alkaline-phosphatase positive colony size in cultures that were stimulated with osteoblast differentiation media. These osteoblast-like cells from ALSKO mice failed to induce osteoclastogenesis of control cells in co-culture assays, indicating that impairment of IGF-1 complex formation with ALS in bone marrow alters cell fate, leading to increased adipogenesis.

Original languageEnglish (US)
Pages (from-to)4709-4714
Number of pages6
JournalJournal of Biological Chemistry
Volume285
Issue number7
DOIs
StatePublished - Feb 12 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fritton, J. C., Kawashima, Y., Mejia, W., Courtland, H. W., Elis, S., Sun, H., Wu, Y., Rosen, C. J., Clemmons, D., & Yakar, S. (2010). The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate. Journal of Biological Chemistry, 285(7), 4709-4714. https://doi.org/10.1074/jbc.M109.041913