Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway

Chen, Zetao, Wu, Chengtie, Gu, Wenyi, Klein, Travis, Crawford, Ross, & Xiao, Yin (2014) Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway. Biomaterials, 35(5), pp. 1507-1518.

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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 b-tricalcium phosphate (b-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 b-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 b-TCP stimulation, indicating that macrophage may participate in the b-TCP stimulated osteogenesis. Interestingly, when macrophageconditioned b-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.

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49 citations in Scopus
48 citations in Web of Science®
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ID Code: 63976
Item Type: Journal Article
Refereed: Yes
Keywords: Macrophage, Immunoreaction, Bone substitute, β-TCP, Osteogenesis
DOI: 10.1016/j.biomaterials.2013.11.014
ISSN: 0142-9612
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomaterials (090301)
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Funding:
Deposited On: 18 Dec 2013 02:55
Last Modified: 09 Apr 2014 12:20

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