title: Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway.
abstract: Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used β-tricalcium phosphate (β-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to β-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the β-TCP stimulation, indicating that macrophage may participate in the β-TCP stimulated osteogenesis. Interestingly, when macrophage-conditioned β-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Zetao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, People's Republic of China. Electronic address: chengtiewu@mail.sic.ac.cn.
authors.forename: Chengtie
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Corner College and Cooper Rds, Brisbane, Queensland 4072, Australia.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Gu
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Travis
authors.initials: T
authors.lastname: Klein
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia. Electronic address: yin.xiao@qut.edu.au.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002130:Calcium Phosphates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008856:Microscopy, Fluorescence; D010012:Osteogenesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D017931:DNA Primers; C485817:beta-tricalcium phosphate
keywords: Bone substitute; Immunoreaction; Macrophage; Osteogenesis; β-TCP