Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss
Artikel i vetenskaplig tidskrift, 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

Författare

Marie Lindberg

Göteborgs universitet

J. Svensson

Göteborgs universitet

K. Venken

Tina Chavoshi

Göteborgs universitet

Niklas Andersson

Göteborgs universitet

Sofia Movérare-Skrtic

Göteborgs universitet

Olle Isaksson

Göteborgs universitet

D. Vanderschueren

Catharina Lindholm

Göteborgs universitet

Claes Ohlsson

Göteborgs universitet

Bone

8756-3282 (ISSN)

Vol. 38 1 85-92

Ämneskategorier

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1016/j.bone.2005.07.027

PubMed

16257281