title: Osteocyte expression of caspase-3, COX-2, IL-6 and sclerostin are spatially and temporally associated following stress fracture initiation.
abstract: Stress fractures (SFxs) are debilitating injuries and exact mechanisms that initiate their repair incompletely understood. We hypothesised that osteocyte apoptosis and expression of cytokines and proteins such as sclerostin, VEGF, TGF-β, COX-2 and IL-6 were early signalling events to facilitate the formation of periosteal woven bone and recruitment of osteoclast precursors to the site of remodelling. A SFx was created in the right ulna of mature female wistar rats using cyclic end loading. Rats were killed 1, 4 and 7 days after loading (n=5 per group). Standard histological staining was used to examine SFx morphology and immunohistochemistry to detect the localisation of these proteins and in situ hybridisation to detect mRNA along the SFx line or gene expression to quantify the target genes. Unloaded ulnae served as controls. The labelling index of caspase-3, COX-2 and IL-6 was significantly elevated in the region of SFxs at all time points compared with controls (P<0.001). In addition, the labelling index of sclerostin protein was significantly reduced in osteocytes adjacent to the SFx region when compared with controls at all three time points (P<0.001). Both VEGF and TGF-β expressions were only localised in the woven bone. These data reinforce the involvement of osteocyte apoptosis in the healing of fatigue damage in bone, and demonstrate that local regulation of sclerostin, COX-2 and IL-6 are important signalling events associated with new bone formation and SFx remodelling.
authors.affiliation: School of Medical Science and Griffith Health Institute, Griffith University, Gold Coast Campus , Gold Coast, Queensland, Australia ; Mater Medical Research Institute, and UQ Translational Research Institute, Mater Hospital , Brisbane, Queensland, Australia.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Wu
authors.affiliation: School of Veterinary Science, The University of Queensland , Gatton, Queensland, Australia.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Kidd
authors.affiliation: School of Veterinary Science, The University of Queensland , Gatton, Queensland, Australia.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Cowling
authors.affiliation: School of Medical Science and Griffith Health Institute, Griffith University, Gold Coast Campus , Gold Coast, Queensland, Australia.
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Kelly
authors.affiliation: School of Medical Science and Griffith Health Institute, Griffith University, Gold Coast Campus , Gold Coast, Queensland, Australia.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Forwood