Although the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) has been identified as a transcriptional coactivator/repressor in various cells, including bone-resorbing osteoclasts, no attention has been paid to its role in bone-forming osteoblasts. Therefore, in this study we show that Ifrd1 is a critical mediator of both osteoblastogenesis and osteoclastogenesis through its expression in osteoblasts. Ifrd1 deficiency enhanced both osteoblast differentiation and maturation, and increased the expression of Runt-related transcription factor 2 and Osterix. A coculture experiment revealed that Ifrd1 deficient osteoblasts have higher osteoprotegerin (OPG) expression and less ability to support osteoclastogenesis. These findings suggest that Ifrd1 plays a pivotal role in bone homeostasis through its expression in osteoblasts, and represents a therapeutic target for bone disease.
Keywords: bone remodeling; osteoblast; osteoclast; transcriptional co-mediator.