The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:285 |
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| Enthalten in: |
The Journal of biological chemistry - 285(2010), 7 vom: 12. Feb., Seite 4709-14 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fritton, J Christopher [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.05.2010 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1074/jbc.M109.041913 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM193731398 |
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| 100 | 1 | |a Fritton, J Christopher |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The insulin-like growth factor-1 binding protein acid-labile subunit alters mesenchymal stromal cell fate |
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| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Kawashima, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Mejia, Wilson |e verfasserin |4 aut | |
| 700 | 1 | |a Courtland, Hayden-Williams |e verfasserin |4 aut | |
| 700 | 1 | |a Elis, Sebastien |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yinjgie |e verfasserin |4 aut | |
| 700 | 1 | |a Rosen, Clifford J |e verfasserin |4 aut | |
| 700 | 1 | |a Clemmons, David |e verfasserin |4 aut | |
| 700 | 1 | |a Yakar, Shoshana |e verfasserin |4 aut | |
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