Fig. 7: VK2 upregulates CBR1 through Nrf2, suppressing PGE2-induced osteoblast ferroptosis.

Upon entering the cell, VK2 can bind to the transcription factor Nrf2, competitively inhibit the binding of Keap1 to Nrf2, and reduce the ubiquitination of Nrf2 caused by Keap1. Nrf2 can bind to the upstream promoter of CBR1 to promote its transcription. As a metabolic enzyme for PGE2, CBR1 can break down PGE2 into PGF2α. PGE2, acting as an inflammatory factor, can promote cell iron death by downregulating the expression of GPX4, FPN, Slc7A11, and upregulating TFRC. Additionally, VK2 can upregulate the expression of ALP, COL1, and RUNX2 in osteoblasts to promote osteoblast differentiation and alleviate osteoporosis.