title: Bone morphogenetic protein-7 enhances bone-tendon integration in a murine in vitro co-culture model.
abstract: OBJECTIVE
  Bone-tendon healing following anterior cruciate ligament reconstruction is reportedly enhanced by bone morphogenetic protein (BMP)-7. To improve our understanding of the underlying biologic processes, we examined the effects of BMP-7 on region-specific gene expression in vitro.
  
  
  METHODS
  A murine in vitro co-culture model simulating the osteoblast, interface and fibroblast regions was established. The dose- and time-dependent region-specific effects of BMP-7 exposure on gene expression of Alpl, Bglap, Col1a1, Runx2 and Spp1 were analysed by quantitative PCR.
  
  
  RESULTS
  At the osteoblast region, BMP-7 significantly increased Alp, Bglap, Col1a1, and Runx2 expression, while Spp1 expression was suppressed. At the interface region, BMP-7 exposure resulted in a trend towards increased expression rates of Alpl and Col1a1, whereas Bglap (P < 0.001) and Runx2 (P < 0.01) were significantly upregulated without any detectable effect on Spp1 expression. At the fibroblast region, BMP-7 increased Alpl (P < 0.001), Bglap (P < 0.001) and Runx2 (P < 0.001) expression, but no significant effects were seen on Col1a1 or Spp1. Exposure to BMP-7 (100 ng/ml) had its most pronounced biologic impact on day ten.
  
  
  CONCLUSIONS
  BMP-7 stimulation showed beneficial region-specific effects on bone-tendon healing in vitro, such as enhanced expression of parameters for ossification and fibroblast transdifferentiation, both key processes during successful graft integration.
authors: Department of Trauma, Hand and Reconstructive Surgery, University of Giessen and Marburg, 35043, Marburg, Germany, schwarti@med.uni-marburg.de.
authors: Tim
authors: T
authors: Schwarting
authors: Michael
authors: M
authors: Benölken
authors: Steffen
authors: S
authors: Ruchholtz
authors: Michael
authors: M
authors: Frink
authors: Philipp
authors: P
authors: Lechler
mesh_terms: D016475:3T3 Cells / Q000502:physiology*; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D001842:Bone and Bones / Q000502:physiology; D018920:Coculture Techniques; D015870:Gene Expression; D066298:In Vitro Techniques; D051379:Mice; D016348:Osseointegration / Q000187:drug effects / Q000235:genetics*; D010006:Osteoblasts / Q000502:physiology*; D013710:Tendons / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
chemical_list: D055419:Bone Morphogenetic Protein 7