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Liver-derived IGF-I...
Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss
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- Lindberg, Marie, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,University of Gothenburg
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- Svensson, J., 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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Venken, K. (author)
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- Chavoshi, Tina, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,University of Gothenburg
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- Andersson, Niklas, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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- Movérare-Skrtic, Sofia (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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- Isaksson, Olle, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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Vanderschueren, D. (author)
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- Carlsten, Hans, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Ohlsson, Claes, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,University of Gothenburg
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- Lindholm, Catharina, 1967 (author)
- Göteborgs universitet,University of Gothenburg
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(creator_code:org_t)
- Elsevier BV, 2006
- 2006
- English.
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In: Bone. - : Elsevier BV. - 8756-3282. ; 38:1, s. 85-92
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Abstract
Subject headings
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- INTRODUCTION: Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. MATERIALS AND METHODS: Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. RESULTS: Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%, P < 0.001), number (-45%, P < 0.01) and thickness (-13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I-/- mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I-/- mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-kappaB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I-/- mice. CONCLUSIONS: Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow.
Keyword
- Acid Phosphatase/metabolism
- Animals
- B-Lymphocytes/drug effects
- Bone Density/drug effects
- Carrier Proteins/metabolism
- Female
- Femur/metabolism/pathology
- Flow Cytometry
- Insulin-Like Growth Factor I/*deficiency/genetics/*physiology
- Isoenzymes/metabolism
- Liver/*metabolism
- Membrane Glycoproteins/metabolism
- Mice
- Mice
- Knockout
- Osteoporosis/etiology/*physiopathology
- Ovariectomy
- Polymerase Chain Reaction
- RANK Ligand
- RNA
- Messenger/analysis
- Receptor Activator of Nuclear Factor-kappa B
- T-Lymphocytes/drug effects
- Tomography
- X-Ray Computed
- Mice
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- ref (subject category)
- art (subject category)
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Lindberg, Marie, ...
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Svensson, J., 19 ...
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Venken, K.
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Chavoshi, Tina, ...
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Andersson, Nikla ...
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Movérare-Skrtic, ...
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Isaksson, Olle, ...
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Vanderschueren, ...
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Carlsten, Hans, ...
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Ohlsson, Claes, ...
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Lindholm, Cathar ...
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- Articles in the publication
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Bone
- By the university
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University of Gothenburg
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Chalmers University of Technology