Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor . Academic Article

abstract

• 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 (PPAR-). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR- 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.

authors

• Dechow, Paul

published proceedings

• Proc Natl Acad Sci U S A

altmetric score

• 10

author list (cited authors)

• Wei, W., Dutchak, P. A., Wang, X., Ding, X., Wang, X., Bookout, A. L., ... Wan, Y.

citation count

• 313

publication date

• January 2012

publisher

• Proceedings of the National Academy of Sciences  Publisher

published in

• Proceedings of the National Academy of Sciences of the United States of America  Journal

keywords

• Adipogenesis
• Animals
• Bone And Bones
• Bone Marrow
• Bone Resorption
• Drug Resistance
• Fibroblast Growth Factors
• Humans
• Mice
• Mice, Knockout
• Organ Size
• Osteoblasts
• Osteogenesis
• Osteoprotegerin
• PPAR Gamma
• RANK Ligand
• Rosiglitazone
• Thiazolidinediones

Digital Object Identifier (DOI)

• 10.1073/pnas.1200797109

start page

• 3143

end page

• 3148

volume

• 109

issue

• 8

URL

• http://dx.doi.org/10.1073/pnas.1200797109