title: Tumor Necrosis Factor Alpha Promotes Osteoclast Formation Via PI3K/Akt Pathway-Mediated Blimp1 Expression Upregulation.
abstract: Tumor necrosis factor alpha (TNF-α)-induced osteoclastogenesis have profound effects in states of inflammatory osteolysis such as rheumatoid arthritis, periprosthetic implant loosening, and periodontitis. However, the exact mechanisms by which TNF-α promotes RANKL-induced osteoclast formation remains poorly understood. B lymphocyte-induced maturation protein-1 (Blimp1) is a transcriptional repressor that plays crucial roles in the differentiation and/or function of various kinds of cells including osteoclasts. A novel mechanism was identified where TNF-α-mediated Blimp1 expression, which contributed to RANKL-induced osteoclastogenesis. It is shown that TNF-α could promote the level of Blimp1 expression during osteoclast differentiation. Silencing of Blimp1 in osteoclast precursor cells obviously attenuated the stimulatory effect of TNF-α on osteoclastogenesis. Mechanistically, TNF-α-induced Blimp1 expression was markedly rescued by blocking the PI3K/Akt signaling pathway, which suggested that PI3K/Akt signaling was involved in the regulation of TNF-α-stimulated Blimp1 expression. Taken together, the results established a molecular mechanism of TNF-α-induced osteoclasts differentiation, and provided insights into the potential contribution of Blimp1 in the regulation of osteoclastogenesis by TNF-α. J. Cell. Biochem. 118: 1308-1315, 2017. © 2016 Wiley Periodicals, Inc.
authors: Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors: LeCheng
authors: L
authors: Wu
authors: Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors: QunFeng
authors: Q
authors: Guo
authors: Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors: Jun
authors: J
authors: Yang
authors: Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors: Bin
authors: B
authors: Ni
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C513258:Prdm1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Blimp1; INFLAMMATORY OSTEOLYSIS; OSTEOCLASTS; PI3K/Akt SIGNALING; TNF-α