title: Macrophage type modulates osteogenic differentiation of adipose tissue MSCs.
abstract: Since the reconstruction of large bone defects remains a challenge, knowledge about the biology of bone healing is desirable to develop novel strategies for improving the treatment of bone defects. In osteoimmunology, macrophages are the central component in the early stage of physiological response after bone injury and bone remodeling in the late stage. During this process, a switch of macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2) is observed. An appealing option for bone regeneration would be to exploit this regulatory role for the benefit of osteogenic differentiation of osteoprogenitor cells (e.g., mesenchymal stem cells; MSCs) and to eventually utilize this knowledge to improve the therapeutic outcome of bone regenerative treatment. In view of this, we focused on the in vitro interaction of different macrophage subtypes with adipose tissue MSCs to monitor the behavior (i.e. proliferation, differentiation and mineralization) of the latter in dedicated co-culture models. Our data show that co-culture of MSCs with M2 macrophages, but not with M1 macrophages or M0 macrophages, results in significantly increased MSC mineralization caused by soluble factors. Specifically, M2 macrophages promoted the proliferation and osteogenic differentiation of MSCs, while M0 and M1 macrophages solely stimulated the osteogenic differentiation of MSCs in the early and middle stages during co-culture. Secretion of the soluble factors oncostatin M (OSM) and bone morphogenetic protein 2 (BMP-2) by macrophages showed correlation with MSC gene expression levels for OSM-receptor and BMP-2, suggesting the involvement of both signaling pathways in the osteogenic differentiation of MSCs.
authors.affiliation: Department of Biomaterials (309), Radboudumc, PO Box 9101, 6500HB, Nijmegen, The Netherlands.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: REPAIR-lab, Institute of Pathology, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Böse
authors.affiliation: REPAIR-lab, Institute of Pathology, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Unger
authors.affiliation: Department of Biomaterials (309), Radboudumc, PO Box 9101, 6500HB, Nijmegen, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.affiliation: REPAIR-lab, Institute of Pathology, Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Charles James
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.affiliation: Department of Biomaterials (309), Radboudumc, PO Box 9101, 6500HB, Nijmegen, The Netherlands. Jeroen.vandenbeucken@radboudumc.nl.
authors.forename: Jeroen J J P
authors.initials: JJJP
authors.lastname: van den Beucken
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic; D002450:Cell Communication; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D016764:Cell Polarity; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D010012:Osteogenesis / Q000235:genetics
chemical_list: D015415:Biomarkers; D016207:Cytokines; D000469:Alkaline Phosphatase
keywords: Cell culture model; MSC; Macrophage; Osteogenic differentiation