| First Author | Zhou Z | Year | 2019 |
| Journal | Int Immunol | Volume | 31 |
| Issue | 4 | Pages | 263-273 |
| PubMed ID | 30779845 | Mgi Jnum | J:273286 |
| Mgi Id | MGI:6286601 | Doi | 10.1093/intimm/dxz002 |
| Citation | Zhou Z, et al. (2019) A high-fat diet aggravates osteonecrosis through a macrophage-derived IL-6 pathway. Int Immunol 31(4):263-273 |
| abstractText | 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. |
