Kruppel-like Factors in Skeletal Physiology and Pathologies

Abstract

Kruppel-like factors (KLFs) belong to a large group of zinc finger-containing transcription factors with amino acid sequences resembling the Drosophila gap gene Krüppel. Since the first report of molecular cloning of the KLF family gene, the number of KLFs has increased rapidly. Currently, 17 murine and human KLFs are known to play crucial roles in the regulation of transcription, cell proliferation, cellular differentiation, stem cell maintenance, and tissue and organ pathogenesis. Recent evidence has shown that many KLF family molecules affect skeletal cells and regulate their differentiation and function. This review summarizes the current understanding of the unique roles of each KLF in skeletal cells during normal development and skeletal pathologies.

The cellular landscape of the endochondral bone during the transition to extrauterine life

“…Notably, the Klf4(+) regulon is detected as active at PN1. Beyond its role in osteogenesis, 70 Klf4 is involved in various cellular processes depending on the cell type and context, and can function as either a pro‐ or anti‐inflammatory factor 71,72 . The Cebpd(+) regulon modulates various cellular processes and is mainly associated with the inflammatory response in macrophages, but it can also act in preventing deleterious effects of the inflammatory response 73 .…”

The cellular landscape of the endochondral bone during the transition to extrauterine life

“…Of note, the Klf4(+) regulon is detected as active at PN1. In addition to its role in osteogenesis (Abe et al, 2022), Klf4 participates in several cellular processes depending on the cellular type and context (Ghaleb and Yang, 2017) and it can act as either a pro- or anti-inflammatory factor (Choi et al, 2018; Kawata et al, 2022; Li et al, 2021; Liao et al, 2011). The Cebpd(+) regulon modulates different cellular processes (Balamurugan and Sterneck, 2013), and is mainly related with inflammatory response in macrophages but can also act in preventing deleterious effects of the inflammatory response (Moore et al, 2012; Rustenhoven et al, 2015).…”

C2H2 proteins: Evolutionary aspects of domain architecture and diversification

“…[44] In addition, a distinct group of specificity proteins (SP) and Krüppel-like factors (KLF) belongs to a highly conserved family of transcription factors that are characterized by three zinc finger C2H2 domains localized in the C-terminus of the proteins. [9,[87][88][89] These groups are important transcription regulators that are involved in a wide range of biological processes, including development, differentiation, proliferation, and metabolism. [87,88,[90][91][92] KLF proteins belong to a family of pioneering transcription factors, which are able to bind to partial motifs exposed on the nucleosomes [93] within condensed chromatin regions.…”