title: In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model.
abstract: 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.
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Welborn Street, Dallas, Texas, 75219.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Phipps
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, 76019.
authors.forename: YiHui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Welborn Street, Dallas, Texas, 75219.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Welborn Street, Dallas, Texas, 75219.|Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kamiya
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Welborn Street, Dallas, Texas, 75219.|Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Naga S
authors.initials: NS
authors.lastname: Adapala
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, 76019.|Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
authors.affiliation: Center for Excellence in Hip Disorders, Texas Scottish Rite Hospital for Children, Welborn Street, Dallas, Texas, 75219.|Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, 75390.
authors.forename: Harry K W
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D058973:Folate Receptors, GPI-Anchored / Q000032:analysis; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications*; D008262:Macrophage Activation; D008297:Male; D008807:Mice, Inbred BALB C; D015336:Molecular Probe Techniques; D018375:Neutrophil Activation; D010020:Osteonecrosis / Q000276:immunology*; D044042:Receptors, Formyl Peptide / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D058973:Folate Receptors, GPI-Anchored; D044042:Receptors, Formyl Peptide; D014409:Tumor Necrosis Factor-alpha
keywords: in vivo monitoring; infrared nanoprobes; innate immune cells; ischemic osteonecrosis; osteoimmunology