The multi-faceted role of retinoid X receptor in bone remodeling

Retinoid X receptors (RXRs) form a unique subclass within the nuclear receptor (NR) superfamily of ligand-dependent transcription factors. RXRs are obligatory partners for a number of other NRs, placing RXRs in a coordinating role at the crossroads of multiple signaling pathways. In addition, RXRs can function as self-sufficient homodimers. Recent advances have revealed RXRs as novel regulators of osteoclastogenesis and bone remodeling. This review outlines the versatility of RXR action in the control of transcription of bone-forming osteoblasts and bone-resorbing osteoclasts, both through heterodimerization with other NRs and through RXR homodimerization. RXR signaling is currently a major therapeutic target and, therefore, knowledge of how RXR signaling affects bone remodeling creates enormous potential for the translation of basic research findings into successful clinical therapies to increase bone mass and improve bone quality.