In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model

Matthew C. Phipps, Yihui Huang, Ryosuke Yamaguchi, Nobuhiro Kamiya, Naga S. Adapala, Liping Tang, Harry K.W. Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)307-313
Number of pages7
JournalJournal of Orthopaedic Research
Volume34
Issue number2
DOIs
Publication statusPublished - Feb 1 2016
Externally publishedYes

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Osteonecrosis
Neutrophils
Macrophages
Inflammation
Bone and Bones
Osteoclasts
Bone Resorption
Osteoblasts
Osteogenesis
Disease Progression
Ischemia
Bone Marrow
Immunohistochemistry
Research

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

Cite this

In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model. / Phipps, Matthew C.; Huang, Yihui; Yamaguchi, Ryosuke; Kamiya, Nobuhiro; Adapala, Naga S.; Tang, Liping; Kim, Harry K.W.

In: Journal of Orthopaedic Research, Vol. 34, No. 2, 01.02.2016, p. 307-313.

Research output: Contribution to journalArticle

Phipps, Matthew C. ; Huang, Yihui ; Yamaguchi, Ryosuke ; Kamiya, Nobuhiro ; Adapala, Naga S. ; Tang, Liping ; Kim, Harry K.W. / In vivo monitoring of activated macrophages and neutrophils in response to ischemic osteonecrosis in a mouse model. In: Journal of Orthopaedic Research. 2016 ; Vol. 34, No. 2. pp. 307-313.
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