Bidirectional optical control of osteogenesis with a light activated vitamin D mimetic

The secosteroid vitamin D is essential for human health maintaining bone metabolism, calcium homeostasis and immune function via the vitamin D receptor (VDR). VDR activation has complex and cell-specific effects in multiple tissues and spatial control of VDR activity is desirable. Here we developed vitD mimetics bearing a photo-switchable azobenzene motif to achieve spatiotemporal resolution in VDR activation. Structure-guided tuning of regiochemistry and H-bonding motifs provided a potent and selective vitD mimetic that can be reversibly switched in cellulo between agonist and antagonist states with light. In a model of osteogenesis, this precision tool mediated light-dependent osteogenic and osteolytic effects corroborating bidirectional optical control of VDR activity.