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.
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. Members of the Fox family respond to metabolic stress in bone tissue, inflammatory signals, hypoxic/oxidative stress, and are associated with aging and autophagy.