Pharmacologic Calcitriol Inhibits Osteoclast Lineage Commitment via the BMP-Smad1 and IκB-NF-κB Pathways.

ABSTRACT: Vitamin D is involved in a range of physiological processes and its active form and analogs have been used to treat diseases such as osteoporosis. Yet how vitamin D executes its function remains unsolved. Here we show that the active form of vitamin D calcitriol increases the peak bone mass in mice by inhibiting osteoclastogenesis and bone resorption. Although calcitriol modestly promoted osteoclast maturation, it strongly inhibited osteoclast lineage commitment from its progenitor monocyte by increasing Smad1 transcription via the vitamin D receptor and enhancing BMP-Smad1 activation, which in turn led to increased IκBα expression and decreased NF-κB activation and NFATc1 expression, with IκBα being a Smad1 target gene. Inhibition of BMP type I receptor or ablation of Bmpr1a in monocytes

SUBMITTER: Li A 

PROVIDER: S-EPMC5814246 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature