Liver X receptors and skeleton: Current state-of-knowledge

The liver X receptors (LXR) is a nuclear receptor that acts as a prominent regulator of lipid homeostasis and inflammatory response. Its therapeutic effectiveness against various diseases like Alzheimer's disease and atherosclerosis has been investigated in detail. Emerging pieces of evidence now reveal that LXR is also a crucial modulator of bone remodeling. However, the molecular mechanisms underlying the pharmacological actions of LXR on the skeleton and its role in osteoporosis are poorly understood. Therefore, in the current review, we highlight LXR and its actions through different molecular pathways modulating skeletal homeostasis. The studies described in this review propound that LXR in association with estrogen, PTH, PPARγ, RXR Hedgehog, and canonical Wnt signaling regulates osteoclastogenesis and bone resorption. It regulates RANKL-induced expression of c-Fos, NFATc1, and NF-κB involved in osteoclast differentiation. Additionally, several studies suggest suppression of RANKL-induced osteoclast differentiation by synthetic LXR ligands. Given the significance of modulation of LXR in various physiological and pathological settings, our findings indicate that therapeutic targeting of LXR might potentially prevent or treat osteoporosis and improve bone quality.

Liver X receptors; Nuclear receptor; Osteoporosis; RANKL.