Open AccessEZH1 Is Associated with TCP-Induced Bone Regeneration through Macrophage Polarization
Author(s) -
Xiaoshi Jia,
Hudi Xu,
Richard J. Miron,
Chengcheng Yin,
Xiaoxin Zhang,
Min Wu,
Yufeng Zhang
Publication year - 2018
Publication title -
stem cells international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.205
H-Index - 64
eISSN - 1687-9678
pISSN - 1687-966X
DOI - 10.1155/2018/6310560
Subject(s) - macrophage polarization , microbiology and biotechnology , macrophage , downregulation and upregulation , nf κb , enhancer , regeneration (biology) , chemistry , biology , signal transduction , gene expression , in vitro , gene , biochemistry
Macrophages have been found to regulate the effects of biomaterials throughout the entire tissue repair process as an antigen-presenting cell. As a well-defined osteoconductive biomaterial for bone defect regeneration, tricalcium phosphate (TCP) has been found to facilitate a favourable osteoimmunomodulatory response that can shift macrophage polarization towards the M2 phenotype. In the present study, our group discovered that a histone methyltransferase enhancer of zeste1 (EZH1) was drastically downregulated in Thp1 cells stimulated by TCP, indicating that EZH1 may participate in the macrophage phenotype shifting. Furthermore, the NF- κ B pathway in macrophages was significantly downregulated through stimulation of TCP, suggesting a potential interaction between EZH1 and the NF- κ B pathway. Utilizing gene knock-down therapy in macrophages, it was found that depletion of EZH1 induced M2 macrophage polarization but did not downregulate NF- κ B. When the NF- κ B pathway was inhibited, the expression of EZH1 was significantly downregulated, suggesting that the inhibition of EZH1 may be regulated by the NF- κ B pathway. These novel findings provide valuable insights into a potential gene target system that controls M2 macrophage polarization which ultimately favours a microenvironment suitable for bone repair.