| First Author | Nistala H | Year | 2010 |
| Journal | J Cell Biol | Volume | 190 |
| Issue | 6 | Pages | 1107-21 |
| PubMed ID | 20855508 | Mgi Jnum | J:165256 |
| Mgi Id | MGI:4836762 | Doi | 10.1083/jcb.201003089 |
| Citation | Nistala H, et al. (2010) Fibrillin-1 and -2 differentially modulate endogenous TGF-beta and BMP bioavailability during bone formation. J Cell Biol 190(6):1107-21 |
| abstractText | Extracellular regulation of signaling by transforming growth factor (TGF)-beta family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-beta and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2-null (Fbn2(-/-)) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2(-/-) phenotype is accounted for by improper activation of latent TGF-beta that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1(-/-) mice exhibit improper latent TGF-beta activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-beta and BMP signaling. |
