title: Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice.
abstract: IL-6 is a pleiotropic cytokine involved in cell signaling in the musculoskeletal system, but its role in bone healing remains uncertain. The purpose of this study was to examine the role of IL-6 in fracture healing. Eight-week-old male C57BL/6 and IL-6 -/- mice were subjected to transverse, mid-diaphyseal osteotomies on the right femora. Sacrifice time points were 1, 2, 4, or 6 weeks post-fracture (N=14 per group). Callus tissue properties was analyzed by microcomputed tomography (micro-CT) and Fourier transform infrared imaging spectroscopy (FT-IRIS). Cartilage and collagen content, and osteoclast density were measured histologically. In intact unfractured bone, IL-6 -/- mice had reduced crystallinity, mineral/matrix ratio, tissue mineral density (TMD), and bone volume fraction (BVF) compared to wildtype mice. This suggests that there was an underlying deficit in baseline bone quality in IL-6 -/- mice. At 2 weeks post-fracture, the callus of IL-6 -/- mice had reduced crystallinity and mineral/matrix ratio. These changes were less evident at 4 weeks. At 2 weeks, the callus of the IL-6 -/- mice had an increased tissue mineral density (TMD), an increased cartilage and collagen content, and reduced osteoclast density compared to these parameters in wildtype mice. By 4 and 6 weeks, these parameters were no longer different between the two strains of mice. In conclusion, IL-6 -/- mice had delayed callus maturity, mineralization, and remodeling compared with the callus of the wildtype mice. These effects were transient indicating that the role of IL-6 appears to be most important in the early stages of fracture healing.
authors.affiliation: The Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Ricciardi
authors.forename: Alexia
authors.initials: A
authors.lastname: Hernandez-Soria
authors.forename: Yuexian
authors.initials: Y
authors.lastname: Shi
authors.forename: Nancy
authors.initials: N
authors.lastname: Pleshko Camacho
authors.forename: Mathias P G
authors.initials: MP
authors.lastname: Bostrom
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology*; D002146:Bony Callus / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D017102:Fracture Healing; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017550:Spectroscopy, Fourier Transform Infrared; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D015850:Interleukin-6