Kruppel-like factor 4 expression in osteoblasts represses osteoblast-dependent osteoclast maturation.

Abstract:

: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.

journal_name

Cell Tissue Res

journal_title

Cell and tissue research

authors

Fujikawa J,Tanaka M,Itoh S,Fukushi T,Kurisu K,Takeuchi Y,Morisaki I,Wakisaka S,Abe M

doi

10.1007/s00441-014-1931-8

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

177-87

issue

1

eissn

0302-766X

issn

1432-0878

journal_volume

358

pub_type

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