Ligand-Independent Actions of Vitamin D Receptor

The study highlighted that the vitamin D receptor (VDR) has ligand-independent actions crucial for maintaining hair follicle homeostasis, beyond its known role in regulating calcium levels and bone integrity. It was observed that mice deficient in 1,25(OH)2D3 had more severe rickets than VDR-null mice, suggesting that unliganded VDR is active. Further research in mice with 1,25(OH)2D3-binding deficient VDRs showed that unliganded VDR represses many genes and causes more severe skeletal and mineral ion defects than VDR-null mice, although only the latter exhibited alopecia. The findings suggested potential treatments using vitamin D analogues for patients with VDR mutations that impair 1,25(OH)2D3 binding.