The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate.
Adipogenesis, Animals, CHO-Cells, Carrier-Proteins, Cell-Differentiation, Cells-Cultured, Cricetinae, Cricetulus, Glycoproteins, Humans, Immunoblotting, Insulin-Like-Growth-Factor-I, Male, Mesenchymal-Stem-Cells, Mice-Inbred-C57BL, Mice-Knockout, Mice-Mutant-Strains, Osteoblasts, Osteoclasts, Polymerase-Chain-Reaction, Protein-Binding
J Biol Chem 2010 Feb; 285(7):4709-14.
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 knock-out (BP3KO) and acid-labile subunit knock-out (ALSKO) mice. We found that expression of the late adipocyte differentiation marker peroxisome proliferator-activated receptor gamma 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.
Fritton, J C.; Kawashima, Y; Mejia, W; Courtland, H W.; Elis, S; Wu, Y; Rosen, C J.; Clemmons, D; and Yakar, S, "The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate." (2010). Faculty Research 2010. 44.