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Kruppel-like factor 4 expression in osteoblasts represses osteoblast-dependent osteoclast maturation
Junji Fujikawa1, Mariko Tanaka, Shousaku Itoh
1Department of Oral Anatomy and Developmental Biology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Cell and Tissue Research
|June 15, 2014
Summary
Kruppel-like factor 4 (KLF4) in osteoblasts inhibits osteoclast maturation and affects bone remodeling. Restoring Runx2 expression partially reverses these KLF4-induced changes in skeletal development.
Area of Science:
- Molecular biology
- Skeletal biology
- Cell biology
Background:
- Kruppel-like factor 4 (KLF4) is a transcription factor involved in skeletal development.
- KLF4 normally represses osteoblast mineralization and down-regulates osteoblastic gene expression.
- Previous studies indicated cell-autonomous effects of KLF4 in osteoblasts.
Purpose of the Study:
- To investigate the non-cell-autonomous effects of KLF4 in osteoblasts on osteoclast maturation.
- To explore the role of KLF4 in regulating cell-matrix interactions during skeletal remodeling.
- To understand the interplay between KLF4 and Runx2 in osteoblast and osteoclast differentiation.
Main Methods:
- Utilized transgenic mice with osteoblastic KLF4 expression.
- Co-cultured wild-type bone marrow-derived macrophages with KLF4-expressing osteoblasts.
- Employed transduction of Runx2 and KLF4 into osteoblasts.
- Analyzed osteoclast formation and extracellular matrix gene expression.
Main Results:
- Transgenic osteoblastic-KLF4 mice exhibited severe defects in osteoclast maturation.
- Co-culture of macrophages with KLF4-expressing osteoblasts reduced multinuclear osteoclast formation.
- Transduction of Runx2 with KLF4 restored KLF4-induced reduction in osteoclastogenesis.
- KLF4 overexpression down-regulated extracellular matrix molecules, partially reversible by Runx2 co-transduction.
Conclusions:
- Osteoblastic KLF4 negatively regulates osteoclast maturation through cell-matrix interactions.
- Regional down-regulation of KLF4 in osteoblasts is crucial for normal skeletal modeling and remodeling.
- Runx2 plays a significant role in mitigating KLF4's effects on osteoclastogenesis and matrix production.
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