title: Retroviral-based gene therapy with cyclooxygenase-2 promotes the union of bony callus tissues and accelerates fracture healing in the rat.
abstract: BACKGROUND
  An in vivo gene therapy strategy was developed to accelerate bone fracture repair.
  
  
  METHODS
  Direct injection of a murine leukemia virus-based vector targeted transgene expression to the proliferating periosteal cells arising shortly after fracture. Cyclooxygenase-2 (Cox-2) was selected because the transgene for its prostaglandin products that promote angiogenesis, bone formation and bone resorption, are all required for fracture healing. The human (h) Cox-2 transgene was modified to remove AU-rich elements in the 3'-untranslated region and to improve protein translation.
  
  
  RESULTS
  In vitro studies revealed robust and sustained Cox-2 protein expression, prostaglandin E(2) and alkaline phosphatase production in rat bone marrow stromal cells and osteoblasts transgenic for the hCox-2 gene. In vivo studies in the rat femur fracture revealed that Cox-2 transgene expression produced bony union of the fracture by 21 days post-fracture, a time when cartilage persisted within the fracture tissues of control animals and approximately 1 week earlier than the healing normally observed in this model. None of the ectopic bone formation associated with bone morphogenetic protein gene therapy was observed.
  
  
  CONCLUSIONS
  This study represents the first demonstration that a single local application of a retroviral vector expressing a single osteoinductive transgene consistently accelerated fracture repair.
authors: Department of Medicine, Loma Linda University, Loma Linda, CA, USA.
authors: Charles H
authors: CH
authors: Rundle
authors: Donna D
authors: DD
authors: Strong
authors: Shin-Tai
authors: ST
authors: Chen
authors: Thomas A
authors: TA
authors: Linkhart
authors: Matilda H-C
authors: MH
authors: Sheng
authors: Jon E
authors: JE
authors: Wergedal
authors: K-H William
authors: KH
authors: Lau
authors: David J
authors: DJ
authors: Baylink
mesh_terms: D000818:Animals; D001483:Base Sequence; D002146:Bony Callus / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015232:Dinoprostone / Q000096:biosynthesis; D005264:Femoral Fractures / Q000235:genetics / Q000628:therapy; D017102:Fracture Healing / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000235:genetics*; D019076:Transgenes
chemical_list: D051546:Cyclooxygenase 2; D015232:Dinoprostone