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

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, whic...