Abstract
Forkhead box (Fox) family, an evolutionarily conserved family of transcription factors carrying the “Forkhead” motif, plays an indispensable role in human health and disease. Fox family genes are involved in cell differentiation, proliferation and apoptosis, embryonic development, aging, glucose and lipid metabolism, and immune regulation. The regulatory role of the Fox family in the context of bone metabolism and orthopedic diseases is an emerging research hotspot. In this review, we highlight the major molecular mechanisms underlying the regulatory role of Fox factors in bone metabolism, bone development, bone homeostasis, and bone diseases associated with inhibition or upregulation of Fox factors. In addition, we discuss the emerging evidence in the realm of Fox factor-based therapeutics.
Highlights
Forkhead box (Fox) family, identified in 2000 (Kaestner et al, 2000), is a group of genes with “Forkhead” motif-dependent transcription factors
We summarize the available evidence of the functional role of the Fox family in the context of bone-associated cell metabolism and various bone diseases (Figure 1)
These findings suggest that deletion of FoxM1 inhibits the ability of osteoclast precursors to differentiate into osteoclasts both in vivo and in vitro
Summary
Fox family, identified in 2000 (Kaestner et al, 2000), is a group of genes with “Forkhead” motif-dependent transcription factors. Recent studies have unraveled the role of Fox family genes as key sensors for bone metabolism. Studies have demonstrated differential expression of Fox factors in osteoblasts in the setting of skeletal disease compared with normal osteoblasts; these differentially expressed factors have been shown to promote or suppress the development of osteoporosis by regulating bone metabolism (Greenblatt et al, 2010; Niedan et al, 2014; Yu et al, 2014; Guan et al, 2015; Hopkins et al, 2016; Zeng et al, 2017). We summarize the available evidence of the functional role of the Fox family in the context of bone-associated cell metabolism and various bone diseases (Figure 1). We highlight the future research directions by identifying related novel biomarkers for cancer diagnosis and therapeutic targets
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