Influence of Seven Ion Species on Osteogenic Differentiation of Mesenchymal Stem Cells Stimulated by Macrophages in Indirect and Direct Coculture Systems

Abstract

Implanted biomaterials release inorganic ions that trigger inflammatory responses, which recruit immune cells whose biochemical signals affect bone tissue regeneration. In this study, we evaluated how mouse macrophages (RAW264, RAW) and mesenchymal stem cells (KUSA-A1, MSCs) respond to seven types of ions (silicon, calcium, magnesium, zinc, strontium, copper, and cobalt) that reportedly stimulate cells related to bone formation. The collagen synthesis, alkaline phosphatase activity, and osteocalcin production of the MSCs varied by ion dose and type after culture in the secretome of RAW cells. However, DNA production was relatively unaffected. The MSC secretome may also stimulate RAW cells in coculture and, therefore, affect osteogenic differentiation of MSCs. Overall, the ions often exerted different effects on each cell type. This study guides future work that explores the mechanisms behind ion-dependent osteogenic differentiation and cell functions.