title: Temporal and Spatial Expression of BMPs and BMP Antagonists During Posterolateral Lumbar Fusion.
abstract: METHODS
  Quantitative gene expression analysis and immunohistochemistry were used to investigate the temporal and spatial expression of bone morphogenic proteins (BMPs) and BMP antagonists in a posterolateral spine fusion model in rabbits.
  
  
  OBJECTIVE
  To identify the expression pattern of BMPs and BMP antagonists and to determine the molecular and histologic changes of the graft and surrounding tissue during fusion.
  
  
  BACKGROUND
  There are no studies on BMP antagonists during spinal fusion. Furthermore, the reciprocal interaction between bone grafts and surrounding tissue is still unknown in fusion.
  
  
  METHODS
  Eighteen New Zealand White rabbits underwent bilateral posterolateral spine fusion with autogenous bone graft. Rabbits were killed at 1, 2, 4, or 6 weeks after arthrodesis. The spinal fusions were analyzed by radiography. On the right side, specimens were collected from the outer zone over the transverse processes, the inner zone between the transverse processes, muscle surrounding bone grafts, and the transverse process. Gene expression of BMP-2, BMP-4, and BMP-7, noggin, chordin, Sox9, and Runx2 were measured by real-time polymerase chain reaction at each time point of each sample. On the left side, molecules of interest were evaluated by immunohistochemistry on tissue sections.
  
  
  RESULTS
  BMP-2, BMP-4, and BMP-7, noggin, and chordin were colocalized in rimming osteoblasts, osteoclasts, and chondrocytes. The outer zone demonstrated earlier bone maturation and faster increase in BMP gene expression than the inner zone. Muscle surrounding bone grafts showed significantly higher BMP expression and Runx2 activity at the early phase. BMP-positive cells were also noted around blood vessels.
  
  
  CONCLUSIONS
  The colocalization and temporal relationship of BMPs and BMP antagonists suggests that BMP activity is tightly regulated by the antagonists during fusion. In addition, not only the decorticated transverse process, but also muscle surrounding bone grafts, is actively involved in osteogenesis during fusion.
authors.affiliation: Department of Orthopaedic Surgery, University of California at Davis Medical Center, Sacramento, CA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Ye
authors.forename: Eric O
authors.initials: EO
authors.lastname: Klineberg
authors.forename: Shane
authors.initials: S
authors.lastname: Curtiss
authors.forename: Sukanta
authors.initials: S
authors.lastname: Maitra
authors.forename: Munish C
authors.initials: MC
authors.lastname: Gupta
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000601:surgery*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013123:Spinal Fusion / Q000379:methods*; D013997:Time Factors; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D055758:SOX9 Transcription Factor; D000099176:Noggin Protein; C054234:chordin