title: Effects of IL-1 receptor-associated kinase-4 gene silencing on human osteoblast-like cells.
abstract: The aim of this study is to identify the effects of interleukin-1 receptor-associated kinase-4 (IRAK-4) gene silencing on human osteoblast-like cells. The siRNA sequences of the target gene, IRAK-4, were constructed and transferred into MG63 cells (control group = MG63 cells; SC group = MG63 cells transfected with scrambled IRAK-4 siRNA; KD group = MG63 cells transfected with 75 nM IRAK-4 siRNA). The morphological changes, cell growth, cell-cycle progression, apoptosis, and the expression of various cytokines and proteins were compared. Compared with the control and SC groups, IRAK-4 gene silencing in MG63 cells caused morphological changes, inhibited growth, altered the cell-cycle distribution, increased apoptosis (p < 0.05), decreased bone alkaline phosphatase and osteocalcin levels (p < 0.05), and decreased protein expression of Bcl-2/Bax and Bcl-2, p-JNK1/2, p-ERK1/2, and p-p38MAPK (p < 0.05). The results indicated that IRAK-4 gene silencing in MG63 cells inhibited cell proliferation and function and increase apoptosis, which may be related to the decreased Bcl-2/Bax ratio and inhibition of the protein expression of various components of the mitogen-activated protein kinase pathways. The results of this study may help improve the understanding of the relationship between IRAK-4 and osteoblast-like cells and the interactions between various cytokines in the periprosthetic inflammatory environment.
authors.affiliation: Department of Orthopedic and Joint Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Zibo
authors.initials: Z
authors.lastname: Yang
authors.forename: Baoding
authors.initials: B
authors.lastname: Huang
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Kang
authors.forename: Ming
authors.initials: M
authors.lastname: Fu
authors.forename: Weiming
authors.initials: W
authors.lastname: Liao
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis / Q000235:genetics; D048688:MAP Kinase Kinase 7 / Q000096:biosynthesis / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C494826:BAX protein, human; D016207:Cytokines; D051028:bcl-2-Associated X Protein; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human