| First Author | Fujikawa J | Year | 2014 |
| Journal | Cell Tissue Res | Volume | 358 |
| Issue | 1 | Pages | 177-87 |
| PubMed ID | 24927920 | Mgi Jnum | J:316280 |
| Mgi Id | MGI:6835085 | Doi | 10.1007/s00441-014-1931-8 |
| Citation | Fujikawa J, et al. (2014) Kruppel-like factor 4 expression in osteoblasts represses osteoblast-dependent osteoclast maturation. Cell Tissue Res 358(1):177-87 |
| abstractText | Kruppel-like factor 4 (KLF4) is a zinc-finger-type transcription factor with a restricted expression pattern during skeletal development. We have previously shown that KLF4 represses osteoblast mineralization concomitant with a down-regulation in the expression of a number of osteoblastic genes, both in vivo and in vitro. In addition to the cell-autonomous effects of KLF4 in osteoblasts, transgenic osteoblastic-KLF4 mice show severe defects in osteoclast maturation. Wild-type bone-marrow-derived macrophages co-cultured with KLF4-expressing osteoblasts exhibit reduced formation of multinuclear osteoclasts as compared with control cultures overexpressing green fluorescent protein. Significantly, the transduction of Runx2, a master regulator of osteoblastogenesis, together with KLF4 into osteoblasts restores the reduction in osteoclastogenesis induced by KLF4 alone. Various extracellular matrix molecules are down-regulated by KLF4 overexpression but this down-regulation can be partially restored by the co-transduction of Runx2. These results suggest that osteoblastic-KLF4 affects osteoclast maturation by regulating cell-matrix interactions and reinforce the importance of the regional down-regulation of KLF4 expression in the subset of osteoblasts for normal skeletal modeling and remodeling. |
