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 journalArticle

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

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Insulin-Like Growth Factor Binding Protein 1
Somatomedins
Mesenchymal Stromal Cells
Knockout Mice
Bone Marrow
Acids
Osteoblasts
Adiposity
Cell culture
Adipocytes
Liver
Bone
Adipogenesis
Insulin-Like Growth Factor Binding Protein 3
Peroxisome Proliferator-Activated Receptors
Differentiation Antigens
Coculture Techniques
Serum
Osteogenesis
Bone Marrow Cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate. / Fritton, J. Christopher; Kawashima, Yuki; Mejia, Wilson; Courtland, Hayden Williams; Elis, Sebastien; Sun, Hui; Wu, Yinjgie; Rosen, Clifford J.; Clemmons, David; Yakar, Shoshana.

In: Journal of Biological Chemistry, Vol. 285, No. 7, 12.02.2010, p. 4709-4714.

Research output: Contribution to journalArticle

Fritton, JC, Kawashima, Y, Mejia, W, Courtland, HW, Elis, S, Sun, H, Wu, Y, Rosen, CJ, 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, vol. 285, no. 7, pp. 4709-4714. https://doi.org/10.1074/jbc.M109.041913
Fritton, J. Christopher ; Kawashima, Yuki ; Mejia, Wilson ; Courtland, Hayden Williams ; Elis, Sebastien ; Sun, Hui ; Wu, Yinjgie ; Rosen, Clifford J. ; Clemmons, David ; Yakar, Shoshana. / The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 7. pp. 4709-4714.
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