Vitamin K is a critical nutrient in the bone metabolism. We have demonstrated that SXR, a nuclear receptor steroid and xenobiotic receptor, expressed in bone cells could be activated by vitamin K_2 as a ligand. vitamin K_2 regulates the expression of various bone-related genes in osteoblastic cells. We have identified novel SXR targets that were up-regulated by vitamin K_2 in human osteoblastic cells. Tsukushi, a small leucine-rich repeat proteoglycan, has been shown to contribute to vitamin K-dependent collagen accumulation. Thus, we have discovered an alternative pathway of vitamin K action in the bone via transcriptional regulation utilizing nuclear receptor SXR.