Proceedings of the National Academy of Sciences - PNAS, 2012-02, Vol.109 (8), p.3143-3148
2012
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- Autor(en) / Beteiligte
- Titel
- Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2012-02, Vol.109 (8), p.3143-3148
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The endocrine hormone fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism and a promising drug for type 2 diabetes. Here we identify FGF21 as a potent regulator of skeletal homeostasis. Both genetic and pharmacologic FGF21 gain of function lead to a striking decrease in bone mass. In contrast, FGF21 loss of function leads to a reciprocal high-bone-mass phenotype. Mechanistically, FGF21 inhibits osteoblastogenesis and stimulates adipogenesis from bone marrow mesenchymal stem cells by potentiating the activity of peroxisome proliferator-activated receptor γ (PPAR-γ). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR-γ agonist rosiglitazone. Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1200797109Titel-ID: cdi_pnas_primary_109_8_3143
- Format
- –
- Schlagworte
- Adipocytes, adipogenesis, Adipogenesis - drug effects, adverse effects, agonists, Animals, Biological Sciences, Bone and Bones - drug effects, Bone and Bones - metabolism, Bone and Bones - pathology, bone density, Bone formation, Bone loss, Bone marrow, Bone Marrow - drug effects, Bone Marrow - pathology, Bone mass, Bone resorption, Bone Resorption - metabolism, Bone Resorption - pathology, Bone turnover, Bones, Diabetes mellitus, Drug Resistance - drug effects, Drugs, Energy metabolism, Fibroblast growth factor, Fibroblast growth factors, Fibroblast Growth Factors - administration & dosage, Fibroblast Growth Factors - metabolism, Fibroblast Growth Factors - pharmacology, Gene expression regulation, glucose, Glucose metabolism, Homeostasis, Hormones, Humans, Lipid metabolism, Mesenchyme, Mice, Mice, Knockout, noninsulin-dependent diabetes mellitus, Organ Size - drug effects, Osteoblastogenesis, Osteoblasts, Osteoblasts - drug effects, Osteoblasts - metabolism, Osteoblasts - pathology, Osteoclasts, Osteogenesis - drug effects, Osteoprotegerin - metabolism, Peroxisome proliferator-activated receptors, phenotype, PPAR gamma - metabolism, RANK Ligand - metabolism, rosiglitazone, Side effects, Stem cells, Thiazolidinediones - pharmacology, Type 2 diabetes mellitus