Steroid and xenobiotic receptor mediates a novel vitamin K-2 signaling pathway in osteoblastic cells

The nuclear receptor steroid and xenobiotic receptor (SXR) is a transcriptional regulator activated by various biological and xenobiotic substances. We have recently shown that SXR is expressed in bone and that this receptor is critical for bone metabolism, particularly in osteoblastic cells. Vitamin K-2, one of the critical nutrients in bone metabolism, has been demonstrated that it is a potent SXR agonist and modulates the expression of various bone-related genes in osteoblastic cells. Using microarray analysis, we identified novel SXR target genes that were activated by vitamin K-2 in osteoblastic cells. Among them, a small leucine-rich repeat proteoglycan, tsukushi, has been shown to contribute to collagen accumulation, and the protein may interact with another vitamin K-2-inducible SXR target, matrilin-2, a member of the matrilin family that functions as collagen adaptors. Besides functioning as a xenobiotic biosensor, our findings show that SXR is also a vitamin K-2 target and an important transcriptional factor that regulates bone homeostasis in bone cells.