The TR4 nuclear receptor belongs to the nuclear receptor superfamily, which is comprised of transcription factors that are related by sequence and structure [
1]. As transcription factors, nuclear receptors control the expression of target genes and thereby direct developmental, physiological, and behavioral responses from the cellular level to that of the whole organism. TR4 is closely related to the TR2, retinoid X receptor, COUP-TF, and HNF4 in sequence and structure [
2], and all of them bind to AGGTCA DNA sequence motifs in direct repeat (DR) orientation, with variable spacing, in the promoters of their target genes [
1,
3‐
6]. Via knocking out TR4 (TR4
−/−), a complex set of phenotypic abnormalities were found to exist in the TR4
−/− mouse, including significant growth retardation [
7], defects in female reproductive function [
8] and maternal behavior [
7], impaired cerebella function [
9,
10], reduced sperm production [
11], and reduced myelination [
12], as well as abnormalities in glucose [
13], lipid metabolism [
14], and foam cell formation [
15].
In this study, we reported that TR4 is involved in regulation of osteoblast activity via regulating osteocalcin expression. TR4 might represent a novel transcriptional factor involved in the bone remodeling network and provide a potential linkage to the pathogenesis of osteoporosis in human disease.