A high-fat diet aggravates osteonecrosis through a macrophage-derived IL-6 pathway. (19th February 2019)

• Record Type: Journal Article
• Authors: Zhou, Zubin; Pan, Chenhao; Wang, Nan; Zhou, Lihui; Shan, Haojie; Gao, Youshui; Yu, Xiaowei
• Is Part Of: International immunology. Volume 31:Number 4(2019)
• Page Start: 263
• Page End: 273
• Publication Date: 2019-02-19
• Subjects: high-fat diet -- IL-6 -- inflammation -- macrophage -- osteonecrosis; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxz002
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract: Inflammation plays an important role in osteonecrosis. Obesity, a risk factor for osteonecrosis, leads to a chronic inflammatory status. We hypothesized that inflammation mediated the effects of obesity on osteonecrosis and tested our hypothesis in a mouse model of osteonecrosis. We fed mice with a high-fat diet (HFD) for 12 weeks before osteonecrosis induction by methylprednisolone and examined bone structure and IL-6 expression. Then we investigated the effects of IL-6 deletion in mice with osteonecrosis on the HFD. Next, we isolated bone marrow cells and determined the cell types responsible for HFD-induced IL-6 secretion. Finally, we investigated the roles of macrophages and macrophage-driven IL-6 in HFD-mediated effects on osteonecrosis and osteogenesis of bone marrow stromal cells (BMSCs). The HFD lead to exacerbated destruction of the femoral head in mice with osteonecrosis and increased IL-6 expression in macrophages. Il-6 knockout or macrophage depletion suppressed the effects of the HFD on bone damage. When co-cultured with macrophages isolated from HFD-fed mice with osteonecrosis, BMSCs showed reduced viability and suppressed osteogenic differentiation. Our results suggest that macrophage-driven IL-6 bridges obesity and osteonecrosis and inhibition of IL-6 or depletion of macrophage may represent a therapeutic strategy for obesity-associated osteonecrosis. Abstract : A high-fat diet exacerbates osteonecrosis via macrophage IL-6