title: The effect of leukemia inhibitory factor on bone in vivo.
abstract: The local effects of leukemia inhibitory factor (LIF) on bone turnover in vivo have been examined. Recombinant murine LIF (0.2 micrograms) or vehicle was injected daily for 5 days over the right hemicalvaria, and the mice were killed on day 6 or 13. Effects on calvarial bone morphology were assessed using quantitative histomorphometry of nondecalcified bone tissue. Increased bone resorption was present in LIF-treated hemicalvaria compared with that in the noninjected hemicalvaria or calvaria from mice injected with vehicle alone at both 6 and 13 days. Significant increases in LIF-treated animals were as follows. Eroded surface increased 10-fold (P = 0.022), osteoclast surface increased 5-fold (P = 0.003), osteoclast numbers increased 3-fold (P = 0.002), and the number of osteoclast nuclei increased 3-fold (P = 0.009). Fibrotic tissue was laid down in the resorption defects, and there was an accompanying thickening of the periosteum (3 times greater in LIF-injected animals; P = 0.003), causing the overall thickness of the treated bones to be almost doubled (P = 0.045). Indices of bone formation were increased in animals treated with LIF. Osteoblast numbers, osteoblast surface, and osteoid area were doubled (P = 0.012, 0.016, and 0.058, respectively). Similar effects of LIF were seen in indomethacin-treated animals. Small but statistically significant morphological changes were also seen in the left noninjected hemicalvariae when LIF-treated animals were compared to controls. LIF increased periosteal area (P = 0.01) and total mineralized bone area (P = 0.002). In conclusion, LIF accelerated bone turnover locally in a prostaglandin-independent manner in normal mice, demonstrating its potential to modify in vivo bone cell function dramatically.
authors.affiliation: Department of Medicine, University of Auckland, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Cornish
authors.forename: K
authors.initials: K
authors.lastname: Callon
authors.forename: A
authors.initials: A
authors.lastname: King
authors.forename: S
authors.initials: S
authors.lastname: Edgar
authors.forename: I R
authors.initials: IR
authors.lastname: Reid
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects*; D005355:Fibrosis; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011994:Recombinant Proteins; D007213:Indomethacin