Macrophage-derived oncostatin M/bone morphogenetic protein 6 in response to Mg-based materials influences pro-osteogenic activity of human umbilical cord perivascular cells.

Abstract

Macrophages are the central immune cell involved in the foreign body reaction to the implants. Furthermore, the magnesium-based materials could modulate macrophage functions, and subsequently influence bone formation via not clearly understood mechanisms. To analysis the roles of materials (magnesium and its gadolinium-based alloy; Mg and Mg-10Gd) on secretion of macrophages and their effects on pro-osteogenic activity, human mesenchymal stem cells (MSC) and macrophages were cocultured directly on the materials surface. Here, oncostatin M (OSM) - glycoprotein 130 (gp130) signaling complex as well as BMP6/SMAD were found to be involved in the Mg and Mg-10Gd multifactorial modulating osteogenic differentiation. Furthermore, materials upregulated the gene expression of bone morphogenetic protein 6 (BMP6) in macrophages, as well as its protein receptors and mothers against decapentaplegic homolog (SMAD) 1/4/5 in cocultured MSC. Besides, both materials could reduce the secretion of tumour necrosis factor alpha (TNFα) and interleukin 1 beta (IL1β) in macrophages and cocultures. These results collectively imply that Mg and Mg-10Gd could create a beneficial microenvironment for osteogenic differentiation and further support Mg-based biomaterial immunomodulatory properties by modulating the interactions of macrophages and MSC for bone regeneration. STATEMENT OF SIGNIFICANCE: Mg-activated macrophages could regulate the pro-osteogenic activity via OSM/gp130 and Smad-related signalling. The neutralisation assay was utilised to confirm the hypothesis of inductive osteoblastic differentiation of human MSC via OSM/gp130 signalling. Current study are essential to evidence that the coordinated communication between macrophages and MSC (OSM/gp130/BMP6/TNFα/IL1β), which could be utilised for improving magnesium-based bone biomaterials and therapeutic applications.