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

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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.