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Effects of Interleukin‐6 Ablation on Fracture Healing in Mice
Author(s) -
Wallace Aaron,
Cooney Timothy E.,
Englund Richard,
Lubahn John D.
Publication year - 2011
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21367
Subject(s) - bone healing , knockout mouse , histology , medicine , osteocalcin , osteoblast , endocrinology , pathology , surgery , chemistry , biochemistry , alkaline phosphatase , receptor , in vitro , enzyme
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. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1437–1442, 2011