Macrophages Inhibit Migration, Metabolic Activity and Osteogenic Differentiation of Human Mesenchymal Stem Cells in vitro

Abstract

To better elucidate the role of macrophages in bone morphogenetic protein (BMP)-induced bone repair, this study evaluated the effects of macrophages on the migration, metabolic activity and BMP-2-induced osteogenic differentiation of human mesenchymal stem cells (hMSCs). Human monocytes were induced into a macrophage phenotype, and the conditioned media (CM) from undifferentiated monocytes and differentiated macrophages were collected for treatment of hMSCs. Expression levels of osteoblastic marker genes, alkaline phosphatase (ALP) activity and mineral deposition were assessed. The migration of hMSCs was significantly decreased after treatment with the macrophage CM (but not monocyte CM), in a dose-dependent manner. Significant inhibition of hMSC metabolism was observed on days 3 and 7 after treatment with the macrophage CM. The osteoblastic marker genes analyzed (ALP, bone sialoprotein, osteocalcin and runt-related transcription factor-2) after exposure of hMSCs to BMP-2 were all significantly downregulated in cells treated with the macrophage CM. The hMSCs treated with macrophage CM showed significantly decreased enzymatic activity of ALP and calcium content compared with those treated with monocyte CM or basal medium. High levels of interleukin-1β and tumor necrosis factor-α found in macrophage CM may mediate these observed effects on hMSCs. We conclude that macrophage CM suppressed the BMP-2-induced osteogenic differentiation of hMSCs, suggesting that macrophages might contribute to decreased osteogenic effects of BMPs in a clinical setting.

Acid and Alkaline Etching of Sandblasted Zirconia Implants: A Histomorphometric Study in Miniature Pigs

“…28,42 The overall situation is controversial as for example monocyte activation can stimulate an osteogenic response 43 but also inhibit migration, metabolic activity and osteogenic differentiation of human mesenchymal stem cells. 44 In the present study, BIC and MIC were found to be associated, suggesting a possible beneficial effect of the macrophages on bone formation. However, keeping the preliminary status of the data in mind, these findings should be an inspiration to further investigate the possible role of macrophages during the osseointegration process.…”

“…While macrophages mediate tissue destruction in situations of chronic inflammation, they also serve as a rich source of growth factors that support wound healing . The overall situation is controversial as for example monocyte activation can stimulate an osteogenic response but also inhibit migration, metabolic activity and osteogenic differentiation of human mesenchymal stem cells . In the present study, BIC and MIC were found to be associated, suggesting a possible beneficial effect of the macrophages on bone formation.…”

Coculture with monocytes/macrophages modulates osteogenic differentiation of adipose‐derived mesenchymal stromal cells on poly(lactic‐co‐glycolic) acid/polycaprolactone scaffolds

“…However, the ADMSCs monoculture showed superficial mineralization on Day 42. Regarding interaction between MSCs and monocytes/ macrophages, several previous studies cocultured macrophages with MSCs and reported diverse effects (i.e., stimulatory or inhibitory) on the osteogenic differentiation of MSCs (C. Chen et al, 2012;Z. Chen et al, 2014;Fernandes et al, 2013;Guihard et al, 2012).…”

“…These macrophages are generally classified as either classically activated macrophages (M1) or alternatively activated macrophages (M2; Murray et al, 2014;Spiller, Freytes, & Vunjak-Novakovic, 2015). Based on current knowledge, M1 macrophages are responsible for angiogenesis and the removal of necrotic tissue at an early stage, whereas M2 macrophages are responsible for immune regulation, matrix deposition, and tissue remodelling at a later stage (C. Chen, Uludag, Wang, Rezansoff, & Jiang, 2012).…”

Immunomodulation regulates mesenchymal stem cell‐based bone regeneration

“…Macrophages are recognized as a highly heterogeneous cell population, and the function of individual populations may vary significantly in vivo (Gordon and Taylor, ; Mosser and Edwards, ). It has been reported that the conditioned medium from differentiated macrophages suppressed the osteogenic differentiation of MSCs and osteoprogenitor cells (Chen et al , ; Lee et al , ). TNF‐ α and IL‐1 β secreted by macrophages were indicated to contribute to these inhibitive effects.…”