Increased adipogenesis in bone marrow but decreased bone mineral density in mice devoid of thyroid hormone receptors.

• Mice deficient for all known thyroid hormone receptors, TRalpha1-/-beta-/- mice, display a clear skeletal phenotype characterized by growth retardation, delayed maturation of long bones and decreased trabecular and total bone mineral density (BMD; -14.6 +/- 2.8%, -14.4 +/- 1.5%). The aim of the present study was to investigate the molecular mechanisms behind the skeletal phenotype in TRalpha1-/-beta-/- mice. Global gene expression analysis was performed on total vertebrae from wild-type (WT) and TRalpha1-/-beta-/- mice using DNA microarray and the results were verified by real-time PCR. The mRNA levels of six genes (AdipoQ, Adipsin, Fat-Specific Protein 27 (FSP 27), lipoprotein lipase (LPL), retinol-binding protein (RBP) and phosphoenolpyruvate carboxykinase (PEPCK)) expressed by mature adipocytes were increased in TRalpha1-/-beta-/- compared with WT mice. An increased amount of fat (225% over WT) due to an increased number but unchanged mean size of adipocytes in the bone marrow of TRalpha1-/-beta-/- mice was revealed. Interestingly, the mRNA levels of the key regulator of osteoclastogenesis, receptor activator of NF-varkappab ligand (RANKL), were dramatically decreased in TRalpha1-/-beta-/- mice. In conclusion, TRalpha1-/-beta-/- mice demonstrated increased expression of adipocyte specific genes and an increased amount of bone marrow fat. Thus, these mice have increased adipogenesis in bone marrow associated with decreased trabecular bone mineral density (BMD). One may speculate that these effects either could be caused by an imbalance in the differentiation of the osteoblast and the adipocyte lineages at the expense of osteoblastogenesis, or by independent effects on the regulation of both osteoblastogenesis and adipogenesis.

Nyckelord

Adipocytes

cytology

metabolism

Adiponectin

Animals

Base Sequence

Body Composition

Bone Density

Bone Marrow

metabolism

Complement Factor D

DNA Primers

Intercellular Signaling Peptides and Proteins

genetics

Lipoprotein Lipase

genetics

Mice

Mice

Knockout

Oligonucleotide Array Sequence Analysis

Phosphoenolpyruvate Carboxykinase (ATP)

genetics

RNA

Messenger

genetics

Receptors

Thyroid Hormone

genetics

physiology

Retinol-Binding Proteins

genetics

Serine Endopeptidases

genetics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)