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

Research output: Contribution to journalArticlepeer-review


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
Issue number7
StatePublished - Feb 12 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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