TY - JOUR
T1 - Transforming growth factor-β1 modulates insulin-like growth factor binding protein-4 expression and proteolysis in cultured periosteal explants
AU - Gonzalez, Carlos
AU - Auw Yang, Kiem G.
AU - Schwab, Joseph H.
AU - Fitzsimmons, James S.
AU - Reinholz, Monica M.
AU - Resch, Zachary T.
AU - Bale, Laurie K.
AU - Clemens, Victoria R.
AU - Conover, Cheryl A.
AU - O'Driscoll, Shawn W.
AU - Reinholz, Gregory G.
N1 - Funding Information:
This study was funded by NIH grant AR43890 and the Mayo Clinic Rochester, Minnesota. Salary support for Dr. Gonzalez was provided by a scholarship from the Mayo Medical School for Graduate Studies. Salary support for Dr. Auw Yang was provided by a fellowship from the University of Utrecht, The Netherlands. The Mayo Medical School Graduate Studies Orthopedics Master’s Program provided salary support for Dr. Schwab.
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Cartilage
KW - Chondrocyte
KW - Insulin-like growth factor binding protein-4
KW - Insulin-like growth factor-I
KW - Periosteum
KW - Pregnancy-associated plasma protein-A
KW - Transforming growth factor beta
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U2 - 10.1016/j.ghir.2009.06.002
DO - 10.1016/j.ghir.2009.06.002
M3 - Article
C2 - 19656700
AN - SCOPUS:77949654120
SN - 1096-6374
VL - 20
SP - 81
EP - 86
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 2
ER -