TGFB1 and neoplasm: Furthermore, PTHrP exerts a paracrine effect on osteoblasts causing enhanced secretion of RANKL which promotes osteoclast differentiation leading to osteolysis, and liberation of insulin like growth factor (IGF) and transforming growth factor beta (TGF-β) promoting a vicious cycle of bone loss and tumor [30,31,32] (Figure 1)