Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Int Immunol. 2019 Mar 28;31(4):263-273. doi: 10.1093/intimm/dxz002.
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.
炎症在骨坏死中起重要作用。肥胖是骨坏死的一个危险因素，导致慢性炎症状态。我们假设炎症介导了肥胖对骨坏死的影响，并在骨坏死的小鼠模型中检验了我们的假设。我们在使用甲泼尼龙诱导骨坏死前，用高脂肪饮食（HFD）喂养小鼠 12 周，并检查了骨结构和 IL-6 表达。然后，我们研究了骨坏死小鼠中 IL-6 缺失对 HFD 的影响。接下来，我们分离骨髓细胞，并确定了负责 HFD 诱导 IL-6 分泌的细胞类型。最后，我们研究了巨噬细胞和巨噬细胞驱动的 IL-6 在 HFD 介导的骨坏死和骨髓基质细胞（BMSC）成骨作用中的作用。HFD 导致骨坏死小鼠的股骨头破坏加剧，并且巨噬细胞中 IL-6 表达增加。Il-6 敲除或巨噬细胞耗竭抑制了 HFD 对骨损伤的影响。当与从 HFD 喂养的骨坏死小鼠中分离的巨噬细胞共培养时，BMSC 的活力降低，成骨分化受到抑制。我们的结果表明，巨噬细胞驱动的 IL-6 连接肥胖和骨坏死，抑制 IL-6 或耗竭巨噬细胞可能代表肥胖相关骨坏死的一种治疗策略。
