Accordingly, HIF-1α silencing by siRNA transfection significantly reduced CXCL12 expression in MC3T3E1 and primary osteoblasts treated with ISO (Fig. 5g), suggesting that β2AR-HIF-1α signaling of osteoblasts may promote tumor cells migration and invasion via upregulation of CXCL12 secretion. Here, CXCL12 is linked to neoplasm.