Monocyte chemoattractant protein-1 and secreted ectodomain of sialic acid-binding Ig-like lectin-9 enhance bone regeneration by inducing M2 macrophages

Abstract

ObjectiveThe bone-healing process consists of a primary inflammatory phase and a subsequent anti-inflammatory bone-forming phase. It was recently suggested that macrophages play an indispensable role in bone healing. Macrophages are plastic immune cells consisting of several subtypes, including pro-inflammatory M1-type and anti-inflammatory M2-type macrophages. Recently, a set of M2 macrophage inducers was described, monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9), and applied them to a rat spinal cord injury model. Here, we hypothesized that MCP-1/sSiglec-9 enhance bone regeneration by inducing M2 macrophages. MethodsWe investigated the osteogenic activity of MCP-1/sSiglec-9 in vitro and in the rat calvarial bone defect model. ResultsWe found that MCP-1/sSiglec-9 induced M2 macrophagesin vitro, which expressed increased levels of multiple mRNAs that encode osteogenic factors, including Igf-1, Tgf-β, Hgf, Bmp2, and Fgf2. We then demonstrated that MCP-1/sSiglec-9 accelerated bone formation and caused anti-inflammatory M2 macrophages to accumulate in the rat calvarial bone defect in vivo. ConclusionsCollectively, our data suggest that the local administration of MCP-1/sSiglec-9 promotes bone formation by inducing anti-inflammatory M2 macrophages that express a variety of osteogenic factors. MCP-1/sSiglec-9 may be beneficial in bone regenerative therapy.