In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model.
Ischemic osteonecrosis (IO) is caused by disruption of the blood supply to bone. It is a debilitating condition with pathological healing characterized by excessive bone resorption and delayed osteogenesis. Although the majority of research has focused on the role of osteoblasts and osteoclasts in the disease progression, we hypothesize that innate immune cells, macrophages and neutrophils, play a significant role. With the recent development of real-time imaging probes for neutrophils and macrophages, the purpose of this study was to investigate the kinetic immune cell response in a mouse model of IO. Our results show that induction of IO leads to a significant accumulation of activated neutrophils and macrophages at the affected tissue by 48 h after surgery. Additionally, the accumulation of these immune cells remained elevated in comparison to sham controls for up to 6 weeks, indicative of chronic inflammation. Immunohistochemistry confirmed the immune cell infiltration into the necrotic bone marrow and the increased presence of TNFα-positive cells, demonstrating, for the first time, a direct response of these cells to ischemia induced necrotic bone. These new findings support a hypothesis that IO is an osteoimmunologic condition where innate immune cells play a significant role in the chronic inflammation.
['Phipps|Matthew C|MC|', 'Huang|YiHui|Y|', 'Yamaguchi|Ryosuke|R|', 'Kamiya|Nobuhiro|N|', 'Adapala|Naga S|NS|', 'Tang|Liping|L|', 'Kim|Harry K W|HK|']
D000818:Animals D004195:Disease Models, Animal D058973:Folate Receptors, GPI-Anchored D007150:Immunohistochemistry D007511:Ischemia D008262:Macrophage Activation D008297:Male D008807:Mice, Inbred BALB C D015336:Molecular Probe Techniques D018375:Neutrophil Activation D010020:Osteonecrosis D044042:Receptors, Formyl Peptide D014409:Tumor Necrosis Factor-alpha
in vivo monitoring ischemic osteonecrosis innate immune cells osteoimmunology infrared nanoprobes