Satb1 promotes osteoclastogenesis by recruiting CBP to upregulate miR-223 expression in chronic kidney disease-mineral and bone disorder.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complex disease which is associated with alterations of bone and mineral metabolism. miR-223 is implicated in both vascular calcification and osteoporosis. In the present study, we investigated the influence of Stab1 gene on miRNA-223 expression in osteoclastogenesis. Differentiation of monocyte/macrophage precursors was assessed by using RAW264.7 cells and peripheral blood mononuclear cells (PBMC). TRAP activity and bone resorption were used to measure osteoclast activity. Overexpression of Satb1 induced a marked increase in osteoclastogenesis in RAW cells (P<0.01) and a decrease in miR-223 expression (P<0.01). In contrast, upregulation of miR-223 increased osteoclastogenesis, as measured by osteoclast number (P<0.01) and TRAP activity (P<0.001). We showed that miR-223 affected the expression of its target genes NFIA and RhoB (P<0.01). Silencing of Satb1 promoted the expression of the osteoclast marker gene OPG and inhibited the expression of NF-κB (P<0.01) and TNF-α (P<0.001). These results were confirmed by measuring bone resorption activity of human PBMC differentiated into osteoclasts where Satb1 suppression inhibited the differentiation of PBMC cells. We have shown that Stab1 modulates osteoclatogenensis by regulating the expression of miR-223. Thus, upregulation of this miRNA to selectively increase osteoclast-like activity in calcified vessels of CKD-MBD could alleviate vascular calcification without altering bone structure.