title: The temporal role of leptin within fracture healing and the effect of local application of recombinant leptin on fracture healing.
abstract: OBJECTIVE
  We hypothesized that leptin is expressed in a specific time sequence during fracture healing, and its deficiency leads to impaired healing.
  
  
  METHODS
  Control (C57BL/6) mice and leptin -/- obese (ob/ob) mice were used. ARM 1:: Fracture callus was harvested at 1, 3, 5, 7, 10, 14, and 21 days (n = 8/time point) after closed middiaphyseal femur fractures were created in 56 C57BL/6 mice, and reverse transcriptase polymerase chain reaction analysis was then performed. Levels of leptin were tracked at each time point listed. ARM 2:: Forty-two C57BL/6 controls and 42 ob/ob mice underwent open stabilized middiaphyseal femur fractures, and tissues were harvested at 14, 21, and 42 days and radiographic, histologic, and quantitative computerized tomography analyses were performed. ARM 3:: Murine recombinant leptin was applied directly at the newly created fracture site in 2 separate groups (10 or 100 μg of leptin) of 42 ob/ob mice. Two-factor analysis of variance and the Student t-test were used for statistical analysis.
  
  
  RESULTS
  The time course of Leptin mRNA expression within a fracture callus was detected. Delay in callus maturation was demonstrated radiographically and histologically in the ob/ob mice. ob/ob fractures had an increase in total callus volume by quantitative computerized tomography (P < 0.05). Application of local leptin at both doses reversed the delay in healing.
  
  
  CONCLUSIONS
  Leptin is expressed in a unique time course during fracture healing and leptin deficiency leads to impaired fracture healing that reverses by local application of leptin.
authors.affiliation: *Department of Orthopaedics, The Ohio State University, Columbus, OH; †Department of Biomedical Engineering; ‡Department of Biomedical Engineering, Center for Molecular and Genomic Imaging; and §Department of Orthopaedic Surgery, University of California, Davis, CA.
authors.forename: Safdar N
authors.initials: SN
authors.lastname: Khan
authors.forename: Grayson
authors.initials: G
authors.lastname: DuRaine
authors.forename: Sohrab S
authors.initials: SS
authors.lastname: Virk
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fung
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rowland
authors.forename: A Hari
authors.initials: AH
authors.lastname: Reddi
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lee
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000000981:diagnostic imaging / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D017102:Fracture Healing / Q000502:physiology*; D020738:Leptin / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D011994:Recombinant Proteins