TGF-β inhibition restores terminal osteoblast differentiation to suppress myeloma growth

多发性骨髓瘤几乎完全在骨髓中发展和扩大，并产生毁灭性的骨骼破坏。在骨髓瘤的骨病变中，转化生长因子-β从骨中释放并被激活，从而抑制成骨细胞的终末分化。转化生长因子-β受体I型激酶抑制剂抑制转化生长因子-β的作用可促进成骨细胞向成熟成骨细胞分化。此外，成熟的成骨细胞抑制骨髓瘤细胞的生长和存活，而未成熟的基质细胞则促进其生长和存活。因此，抑制转化生长因子-β信号可能成为治疗骨髓瘤细胞生长和破坏性骨损伤的新靶点。

Multiple myeloma develops and expands almost exclusively in the bone marrow, and generates devastating bone destruction. In bone lesions in myeloma, TGF-β is released from the bone and activated, which suppresses terminalosteoblast differentiation. Inhibition of TGF-β actions by TGF-β receptor type I kinase inhibitor enhances osteoblastic differentiation to mature osteoblasts. Furthermore, mature osteoblasts inhibit, while immature stromal cells enhance, myeloma cell growth and survival. Thus, inhibition of TGF-β signal may become a new therapeutic target against myeloma cell growth and destructive bone lesions.