 In the endosteum, Tie-2/Ang-1 signaling is predominantly expressed by osteoblastic cells.Although which specific TIE receptors mediate signals downstream of angiogenesis stimulation is highly contested, it is clear that TIE-2 is capable of activation as a result of binding angiopoietins.Angiopoietin proteins 1 through 4 are all ligands for Tie-2 receptors.