title: Bone morphogenetic protein 7 (BMP-7) influences tendon-bone integration in vitro.
abstract: BACKGROUND
  Successful graft ingrowth following reconstruction of the anterior cruciate ligament is governed by complex biological processes at the tendon-bone interface. The aim of this study was to investigate in an in vitro study the effects of bone morphogenetic protein 7 (BMP-7) on tendon-bone integration.
  
  
  METHODS
  To study the biological effects of BMP-7 on the process of tendon-bone-integration, two independent in vitro models were used. The first model involved the mono- and coculture of bovine tendon specimens and primary bovine osteoblasts with and without BMP-7 exposure. The second model comprised the mono- and coculture of primary bovine osteoblasts and fibroblasts. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lactate and osteocalcin (OCN) were analyzed by ELISA. Histological analysis and electron microscopy of the tendon specimens were performed.
  
  
  RESULTS
  In both models, positive effects of BMP-7 on ALP enzyme activity were observed (p<0.001). Additionally, similar results were noted for LDH activity and lactate concentration. BMP-7 stimulation led to a significant increase in OCN expression. Whereas the effects of BMP-7 on tendon monoculture peaked during an early phase of the experiment (p<0.001), the cocultures showed a maximal increase during the later stages (p<0.001). The histological analysis showed a stimulating effect of BMP-7 on extracellular matrix formation. Organized ossification zones and calcium carbonate-like structures were only observed in the BMP-stimulated cell cultures.
  
  
  CONCLUSIONS
  This study showed the positive effects of BMP-7 on the biological process of tendon-bone integration in vitro. Histological signs of improved mineralization were paralleled by increased rates of osteoblast-specific protein levels in primary bovine osteoblasts and fibroblasts.
  
  
  CONCLUSIONS
  Our findings indicated a role for BMP-7 as an adjuvant therapeutic agent in the treatment of ligamentous injuries, and they emphasized the importance of the transdifferentiation process of tendinous fibroblasts at the tendon-bone interface.
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Tim
authors: T
authors: Schwarting
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Philipp
authors: P
authors: Lechler
authors: Department of Orthopaedics and Rheumatology, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Johannes
authors: J
authors: Struewer
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Marius
authors: M
authors: Ambrock
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Thomas Manfred
authors: TM
authors: Frangen
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Steffen
authors: S
authors: Ruchholtz
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Ewgeni
authors: E
authors: Ziring
authors: Department of Trauma, Hand- and Reconstructive Surgery, University Hospital Giessen and Marburg, Marburg, Germany.
authors: Michael
authors: M
authors: Frink
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects*; D002417:Cattle; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D013710:Tendons / Q000166:cytology* / Q000187:drug effects*; D019737:Transplants
chemical_list: D055419:Bone Morphogenetic Protein 7; D015675:Osteocalcin; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase
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