title: BMP4 localization and PCNA expression during distraction osteogenesis of the porcine mandible.
abstract: This study characterized sequential molecular and cellular events in the porcine mandibular distraction osteogenesis (DO) wound. Nineteen Yucatan minipigs were divided into three treatment groups: Group A, unilateral mandibular distraction with 0 day latency, 1mm/day rate for 12 days, 24 days fixation (n=16); Group B, acute lengthening 12 mm (n=2); Group C, sham control (n=1). Group A was further divided by death date: mid-DO (n=5), end-DO (n=4), mid-fixation (n=5) and end-fixation (n=2). Groups B and C were killed on postoperative day 36, corresponding to end-fixation. Specimens were stained for proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-4 (BMP4). Cellular proliferation (PCNA) was assessed quantitatively and BMP4 staining was assessed on a semi-quantitative scale. Progenitor cell proliferation was greatest during mid-DO and decreased from end-DO through end-fixation. Proliferation in the acute lengthening group was elevated relative to sham control and comparable to end-DO. BMP4 staining intensity (localized to the periosteal cambium layer) was greatest during mid- and end-DO, decreased at mid-fixation and was undetectable at end-fixation. Progenitor cell proliferation and BMP4 expression are greatest during mid-DO and decrease progressively thereafter. At the time of death of the acute lengthening group, only increased cell proliferation was demonstrated.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Hansen
authors.forename: M E
authors.initials: ME
authors.lastname: Lawler
authors.forename: W B
authors.initials: WB
authors.lastname: Williams
authors.forename: M J
authors.initials: MJ
authors.lastname: Troulis
authors.forename: L B
authors.initials: LB
authors.lastname: Kaban
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000032:analysis*; D049109:Cell Proliferation; D004396:Coloring Agents; D005260:Female; D007150:Immunohistochemistry; D016268:Internal Fixators; D008334:Mandible / Q000473:pathology / Q000601:surgery*; D010006:Osteoblasts / Q000473:pathology; D019857:Osteogenesis, Distraction / Q000295:instrumentation / Q000379:methods*; D010521:Periosteum / Q000473:pathology / Q000601:surgery; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D011897:Random Allocation; D013234:Stem Cells / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors
chemical_list: D055415:Bone Morphogenetic Protein 4; D004396:Coloring Agents; D018809:Proliferating Cell Nuclear Antigen