Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss
Journal article, 2006
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.
Mice
Female
Isoenzymes/metabolism
Receptor Activator of Nuclear Factor-kappa B
RANK Ligand
X-Ray Computed
Membrane Glycoproteins/metabolism
Tomography
Knockout
RNA
Mice
Bone Density/drug effects
Insulin-Like Growth Factor I/*deficiency/genetics/*physiology
Flow Cytometry
Femur/metabolism/pathology
Ovariectomy
Acid Phosphatase/metabolism
B-Lymphocytes/drug effects
Osteoporosis/etiology/*physiopathology
T-Lymphocytes/drug effects
Animals
Carrier Proteins/metabolism
Polymerase Chain Reaction
Messenger/analysis
Liver/*metabolism
Author
Marie Lindberg
University of Gothenburg
J. Svensson
University of Gothenburg
K. Venken
Tina Chavoshi
University of Gothenburg
Niklas Andersson
University of Gothenburg
Sofia Movérare-Skrtic
University of Gothenburg
Olle Isaksson
University of Gothenburg
D. Vanderschueren
Catharina Lindholm
University of Gothenburg
Claes Ohlsson
University of Gothenburg
Bone
8756-3282 (ISSN)
Vol. 38 1 85-92Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1016/j.bone.2005.07.027
PubMed
16257281