Murine Model of Progressive Orthopedic Wear Particle-Induced Chronic Inflammation and Osteolysis

Jukka Pajarinen, Akira Nabeshima, Tzu Hua Lin, Taishi Sato, Emmanuel Gibon, Eemeli Jämsen, Laura Lu, Karthik Nathan, Zhenyu Yao, Stuart B. Goodman

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Periprosthetic osteolysis and subsequent aseptic loosening of total joint replacements are driven by byproducts of wear released from the implant. Wear particles cause macrophage-mediated inflammation that culminates with periprosthetic bone loss. Most current animal models of particle-induced osteolysis are based on the acute inflammatory reaction induced by wear debris, which is distinct from the slowly progressive clinical scenario. To address this limitation, we previously developed a murine model of periprosthetic osteolysis that is based on slow continuous delivery of wear particles into the murine distal femur over a period of 4 weeks. The particle delivery was accomplished by using subcutaneously implanted osmotic pumps and tubing, and a hollow titanium rod press-fit into the distal femur. In this study, we report a modification of our prior model in which particle delivery is extended to 8 weeks to better mimic the progressive development of periprosthetic osteolysis and allow the assessment of interventions in a setting where the chronic particle-induced osteolysis is already present at the initiation of the treatment. Compared to 4-week samples, extending the particle delivery to 8 weeks significantly exacerbated the local bone loss observed with μCT and the amount of both peri-implant F4/80+ macrophages and tartrate-resistant acid phosphatase-positive osteoclasts detected with immunohistochemical and histochemical staining. Furthermore, systemic recruitment of reporter macrophages to peri-implant tissues observed with bioluminescence imaging continued even at the later stages of particle-induced inflammation. This modified model system could provide new insights into the mechanisms of chronic inflammatory bone loss and be particularly useful in assessing the efficacy of treatments in a setting that resembles the clinical scenario of developing periprosthetic osteolysis more closely than currently existing model systems.

Original languageEnglish
Pages (from-to)1003-1011
Number of pages9
JournalTissue Engineering - Part C: Methods
Volume23
Issue number12
DOIs
Publication statusPublished - Dec 2017

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

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