Transforming growth factor-β1 modulates insulin-like growth factor binding protein-4 expression and proteolysis in cultured periosteal explants

Carlos Gonzalez, Kiem G. Auw Yang, Joseph H. Schwab, James S. Fitzsimmons, Monica M. Reinholz, Zachary T. Resch, Laurie K. Bale, Victoria R. Clemens, Cheryl A. Conover, Shawn W. O'Driscoll, Gregory G. Reinholz

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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-β) 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-β signaling during periosteal chondrogenesis. The purpose of this study was to determine the effect of TGF-β1 on IGF binding protein-4 (IGFBP-4) and the IGFBP-4 protease pregnancy-associated plasma protein-A (PAPP-A) expression in cultured periosteal explants. Design: Periosteal explants from rabbits were cultured with or without TGF-β1. 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-β1-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-β1-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 10. days of culture (the onset of cartilage formation in this model) in conditioned medium from TGF-β1-treated explants. Conclusions: This study demonstrates that TGF-β1 modulates the expression of IGFBP-4 and PAPP-A in cultured periosteal explants.

Original languageEnglish (US)
Pages (from-to)81-86
Number of pages6
JournalGrowth Hormone and IGF Research
Issue number2
StatePublished - Apr 2010


  • Cartilage
  • Chondrocyte
  • Insulin-like growth factor binding protein-4
  • Insulin-like growth factor-I
  • Periosteum
  • Pregnancy-associated plasma protein-A
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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