| First Author | Bunn RC | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 325 |
| Issue | 3 | Pages | 698-706 |
| PubMed ID | 15541345 | Mgi Jnum | J:93810 |
| Mgi Id | MGI:3505798 | Doi | 10.1016/j.bbrc.2004.10.092 |
| Citation | Bunn RC, et al. (2004) IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts. Biochem Biophys Res Commun 325(3):698-706 |
| abstractText | Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzincin pregnancy-associated plasma protein (PAPP)-A. Degradation of IGFBP-4 by PAPP-A or MC3T3-E1 conditioned medium was enhanced by IGF-II but inhibited by mutation of basic residues at or near the PAPP-A cleavage site in IGFBP-4. Furthermore, immunodepletion of PAPP-A from MC3T3-E1 conditioned medium abolished IGFBP-4 degradation. We also found that PAPP-A messenger RNA was expressed throughout differentiation of MC3T3-E1 cells. These results demonstrate for the first time that PAPP-A is the IGFBP-4 protease in MC3T3-E1 cells, a widely used model for osteoblast development, and that PAPP-A may regulate IGF release throughout osteoblast differentiation. |
