title: Effects of interleukin-6 ablation on fracture healing in mice.
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.
authors: Penn State Hershey Medical Center, Hershey, Pennsylvania, USA.
authors: Aaron
authors: A
authors: Wallace
authors: Timothy E
authors: TE
authors: Cooney
authors: Richard
authors: R
authors: Englund
authors: John D
authors: JD
authors: Lubahn
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002146:Bony Callus / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004548:Elasticity / Q000502:physiology; D017102:Fracture Healing / Q000235:genetics*; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015675:Osteocalcin / Q000378:metabolism; D013314:Stress, Mechanical; D000071681:Tartrate-Resistant Acid Phosphatase; D013978:Tibial Fractures / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015850:Interleukin-6; D007527:Isoenzymes; D015675:Osteocalcin; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase