Macrophages derived from THP-1 promote the osteogenic differentiation of mesenchymal stem cells through the IL-23/IL-23R/β-catenin pathway

Abnormal bone formation is a clinically significant dilemma for many conditions in response to injury, inflammation or genetic disease. However, the effects of inflammation on the osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. IL-23 secretion from macrophages might contribute to the development of bone formation. Here, we investigated the stimulatory effects of THP-1 macrophage conditioned medium (M Phi CM) on the osteogenic differentiation of human MSCs and the associated signaling pathways. The osteogenic differentiation of MSCs was induced after exposure to osteogenic differentiation medium (OM). M Phi CM significantly increased alkaline phosphate (ALP) activity and calcium mineralization in MSCs. Osteogenic marker genes, including RUNX2, ALP and osteocalcin (OCN), were also up-regulated in MSCs after exposure to M Phi CM. Moreover, western blotting revealed that M Phi CM treatment induced STAT3 and P-catenin activation in MSCs. Furthermore, blockade of IL-23 in M Phi CM not only impaired the osteogenic-promotion effects of macrophage but also decreased the expression of osteogenic maker genes. However, IL-23R silencing suppressed M Phi CM-induced calcium mineralization and osteogenic maker gene expression in MSCs. These data suggest that macrophages derived from THP-1 promote the osteoblastic differentiation of MSCs through the IL-23/IL-23R/beta-catenin pathway and macrophages might contribute to the development of bone formation in inflammation. (C) 2015 Elsevier Inc. All rights reserved.