Effects of interleukin-6 ablation on fracture healing in mice

Aaron Wallace, Timothy E. Cooney, Richard B. Englund, John D. Lubahn

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40 Scopus citations

Abstract

This study examined the impact of an interleukin-6 (IL-6) knockout on fracture healing in terms of histological and biomechanical responses. Following IACUC approval, tibial fractures were produced in 4- to 6-week-old IL-6 knockouts (n = 35) and wild-type mice (n = 36) and harvested along with contralateral limbs at 2 and 6 weeks postsurgery. Histology quantified stage of healing, lymphocyte infiltration, TRAP+ cells, and osteocalcin deposition. Bend testing established maximum load and stiffness. Based on normality assessments, Mann-Whitney U or independent t-tests were used for data analysis using a p-value threshold of 0.05. Stage of healing, lymphocyte infiltration, and osteocalcin deposition were similar for all time points (p ≥ 0.243). TRAP+ cell counts were reduced approximately 10-fold in the knockout at 2 weeks (p = 0.015) but were similar at 6 weeks (p = 0.689). Force-to-failure in knockouts was approximately 40% that of wild-type mice at 2 weeks (p = 0.040) but similar at 6 weeks (p = 0.735). Knockout bone was about 25% less stiff at 2 weeks but approximately 60% stiffer at 6 weeks (p ≥ 0.110). The absence of IL-6 during early fracture healing significantly reduced osteoclastogenesis and impaired callus strength. By 6 weeks, most histological and biomechanical parameters were similar to fractures in wild-type bone.

Original languageEnglish (US)
Pages (from-to)1437-1442
Number of pages6
JournalJournal of Orthopaedic Research
Volume29
Issue number9
DOIs
Publication statusPublished - Sep 1 2011

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All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

Cite this

Wallace, A., Cooney, T. E., Englund, R. B., & Lubahn, J. D. (2011). Effects of interleukin-6 ablation on fracture healing in mice. Journal of Orthopaedic Research, 29(9), 1437-1442. https://doi.org/10.1002/jor.21367