title: Uncoupled angiogenesis and osteogenesis in nicotine-compromised bone healing.
abstract: Nicotine is the main chemical component responsible for tobacco addiction. This study aimed to evaluate the influence of nicotine on angiogenesis and osteogenesis and the associated expression of angiogenic and osteogenic mediators during bone healing. Forty-eight adult New Zealand White rabbits were randomly assigned to a nicotine group and a control group. Nicotine pellets (1.5 g, 60-day time release) or placebo pellets were implanted in the neck subcutaneous tissue. The nicotine or placebo exposure time for all the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Eight animals in each group were euthanized on day 5, day 11 of active distraction, and week 1 of consolidation, respectively. The mandibular samples were subjected to radiographic, histologic, immunohistochemical, and real-time reverse-transcriptase polymerase chain reaction examinations. Nicotine exposure upregulated the expression of hypoxia inducible factor 1alpha and vascular endothelial growth factor and enhanced angiogenesis but inhibited the expression of bone morphogenetic protein 2 and impaired bone healing. The results indicate that nicotine decouples angiogenesis and osteogenesis in this rabbit model of distraction osteogenesis, and the enhanced angiogenesis cannot compensate for the adverse effects of nicotine on bone healing.
authors.affiliation: Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Hong Kong, Hong Kong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Li Wu
authors.initials: LW
authors.lastname: Zheng
authors.forename: Mai Har
authors.initials: MH
authors.lastname: Sham
authors.forename: Lim Kwong
authors.initials: LK
authors.lastname: Cheung
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D001842:Bone and Bones / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology*; D019857:Osteogenesis, Distraction; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011859:Radiography; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
chemical_list: D055396:Bone Morphogenetic Protein 2; D024141:Collagen Type IV; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D009538:Nicotine