| First Author | Wei W | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 8 | Pages | 3143-8 |
| PubMed ID | 22315431 | Mgi Jnum | J:182005 |
| Mgi Id | MGI:5314567 | Doi | 10.1073/pnas.1200797109 |
| Citation | Wei W, et al. (2012) Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma. Proc Natl Acad Sci U S A 109(8):3143-8 |
| abstractText | 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 gamma (PPAR-gamma). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR-gamma 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. |
