title: Transforming growth factor-beta1 modulates insulin-like growth factor binding protein-4 expression and proteolysis in cultured periosteal explants.
abstract: OBJECTIVE
  Periosteum is involved in bone growth and fracture healing and has been used as a cell source and tissue graft for tissue engineering and orthopedic reconstruction including joint resurfacing. Periosteum can be induced by transforming growth factor beta (TGF-beta) or insulin-like growth factor-I (IGF-I) alone or in combination to form cartilage. However, little is known about the interaction between IGF and TGF-beta signaling during periosteal chondrogenesis. The purpose of this study was to determine the effect of TGF-beta1 on IGF binding protein-4 (IGFBP-4) and the IGFBP-4 protease pregnancy-associated plasma protein-A (PAPP-A) expression in cultured periosteal explants.
  
  
  METHODS
  Periosteal explants from rabbits were cultured with or without TGF-beta1. IGFBP-4 and PAPP-A mRNA levels were determined by real-time quantitative PCR. Conditioned medium was analyzed for IGFBP-4 and PAPP-A protein levels and IGFBP-4 protease activity.
  
  
  RESULTS
  TGF-beta1-treated explants contained lower IGFBP-4 mRNA levels throughout the culture period with a maximum reduction of 70% on day 5 of culture. Lower levels of IGFBP-4 protein were also detected in the conditioned medium from TGF-beta1-treated explants. PAPP-A mRNA levels were increased 1.6-fold, PAPP-A protein levels were increased threefold, and IGFBP-4 protease activity was increased 8.5-fold between 7 and 10days of culture (the onset of cartilage formation in this model) in conditioned medium from TGF-beta1-treated explants.
  
  
  CONCLUSIONS
  This study demonstrates that TGF-beta1 modulates the expression of IGFBP-4 and PAPP-A in cultured periosteal explants.
authors: Cartilage and Connective Tissue Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors: Carlos
authors: C
authors: Gonzalez
authors: Kiem G
authors: KG
authors: Auw Yang
authors: Joseph H
authors: JH
authors: Schwab
authors: James S
authors: JS
authors: Fitzsimmons
authors: Monica M
authors: MM
authors: Reinholz
authors: Zachary T
authors: ZT
authors: Resch
authors: Laurie K
authors: LK
authors: Bale
authors: Victoria R
authors: VR
authors: Clemens
authors: Cheryl A
authors: CA
authors: Conover
authors: Shawn W
authors: SW
authors: O'Driscoll
authors: Gregory G
authors: GG
authors: Reinholz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics* / Q000378:metabolism*; D009924:Organ Culture Techniques; D010521:Periosteum / Q000187:drug effects* / Q000378:metabolism*; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology* / Q000502:physiology
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D011266:Pregnancy-Associated Plasma Protein-A