| First Author | El-Hoss J | Year | 2014 |
| Journal | Gene | Volume | 533 |
| Issue | 1 | Pages | 246-52 |
| PubMed ID | 24095779 | Mgi Jnum | J:206620 |
| Mgi Id | MGI:5551563 | Doi | 10.1016/j.gene.2013.09.074 |
| Citation | El-Hoss J, et al. (2014) Inactivation of the integrin-linked kinase (ILK) in osteoblasts increases mineralization. Gene 533(1):246-52 |
| abstractText | In osteoblasts, Integrin-Linked Kinase (ILK)-dependent phosphorylation of the cJUN transcriptional coactivator, alphaNAC, induces the nuclear accumulation of the coactivator and potentiates cJUN-dependent transcription. Mutation of the ILK phosphoacceptor site within the alphaNAC protein leads to cytoplasmic retention of the coactivator and cell-autonomous increases in osteoblastic activity. In order to gain further insight into the ILK-alphaNAC signaling cascade, we inactivated ILK using RNA knockdown in osteoblastic cells and engineered mice with specific ablation of ILK in osteoblasts. ILK knockdown in MC3T3-E1 osteoblast-like cells reduced phosphorylation of its downstream target glycogen synthase kinase 3beta (GSK3beta), which led to cytoplasmic retention of alphaNAC and increased mineralization with augmented expression of the osteoblastic differentiation markers, pro-alpha1(I) collagen (col1A1), Bone Sialoprotein (Bsp) and Osteocalcin (Ocn). Cultured ILK-deficient primary osteoblasts also showed increased cytoplasmic alphaNAC levels, and augmented mineralization with higher Runx2, Col1a1 and Bsp expression. Histomorphometric analysis of bones from mutant mice with ILK-deficient osteoblasts (Col1-Cre;Ilk(-/fl)) revealed transient changes, with increased bone volume in newborn animals that was corrected by two weeks of age. Our data suggest that the ILK-alphaNAC cascade acts to reduce the pace of osteoblast maturation. We propose that in vivo, functional redundancy is able to compensate for the loss of ILK activity, leading to the absence of an obvious phenotype when osteoblast-specific Ilk-deficient mice reach puberty. |
