scholarly journals Matrix Metalloproteinase-dependent Activation of Latent Transforming Growth Factor-β Controls the Conversion of Osteoblasts into Osteocytes by Blocking Osteoblast Apoptosis

2002 ◽  
Vol 277 (46) ◽  
pp. 44061-44067 ◽  
Author(s):  
Morten A. Karsdal ◽  
Lykke Larsen ◽  
Michael T. Engsig ◽  
Henriette Lou ◽  
Mercedes Ferreras ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Osteoblast Apoptosis

Transforming growth factor-β prevents osteoblast apoptosis induced by skeletal unloading via PI3K/Akt, Bcl-2, and phospho-Bad signaling

2008 ◽  
Vol 294 (4) ◽  
pp. E794-E801 ◽  
Author(s):  
Cécilie Dufour ◽  
Xavier Holy ◽  
Pierre J. Marie
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Protective Role ◽  
Akt Signaling ◽  
Hindlimb Suspension ◽  
Skeletal Unloading ◽  
Continuous Administration ◽  
Osteoblast Apoptosis

Loss of mechanical loading induces rapid bone loss resulting from reduced osteoblastogenesis and decreased bone formation. The signaling mechanisms involved in this deleterious effect on skeletal metabolism remain poorly understood. We have previously shown that hindlimb suspension in rats increases osteoblast apoptosis associated with decreased phosphatidylinositol 3-kinase (PI3K) signaling. In this study, we investigated whether transforming growth factor (TGF)-β2 may prevent the altered signaling and osteoblast apoptosis induced by skeletal unloading in vivo. Hindlimb suspension-induced decreased bone volume was associated with reduced α5β1-integrin protein levels and PI3K/Akt signaling in unloaded bone. Continuous administration of TGF-β2 using osmotic minipumps prevented the decreased α5β1-integrin expression and the reduced PI3K/Akt signaling in unloaded bone, resulting in the prevention of osteoblast apoptosis. We also show that TGF-β2 prevented the decreased Bcl-2 levels induced by unloading, which suggests that TGF-β2 targets Bcl-2 via PI3K/Akt to prevent osteoblast apoptosis in unloaded bone. Furthermore, we show that TGF-β2 prevented the decrease in phosphorylated Bad, the inactive form of the proapoptotic protein Bad, induced by unloading. These results identify a protective role for TGF-β2 in osteoblast apoptosis induced by mechanical unloading via the α5β1/PI3K/Akt signaling cascade and downstream Bcl-2 and phospho-Bad survival proteins. We thus propose a novel role for TGF-β2 in protection from unloading-induced apoptosis in vivo.

High Glucose Decreases Matrix Metalloproteinase-2 Activity in Rat Mesangial Cells via Transforming Growth Factor-β1

2001 ◽  
Vol 9 (4) ◽  
pp. 249-257 ◽  
Author(s):  
Rekha Singh ◽  
Ruo Hua Song ◽  
Nahid Alavi ◽  
Alfredo A. Pegoraro ◽  
Ashok K. Singh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β ◽  
Matrix Metalloproteinase 2
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