title: Bone morphogenetic protein (BMP)-2 induces apoptosis in human myeloma cells.
abstract: BMPs (bone morphogenetic proteins), members of the transforming growth factor (TGF)-beta superfamily, are a group of related proteins which are capable of inducing the formation of cartilage and bone, but are now regarded as multifunctional cytokines. However, little is known about their role in hematopoiesis. Recently, we found a novel function of BMPs to hematopoietic cells in that BMP-2 induces apoptosis not only in human myeloma cell lines, but also in primary samples from patients with multiple myeloma in vitro. BMP-2 caused cell cycle arrest in the G1 phase which was associated with accumulation of p21CIP1/WAF1 and p27KIP1, and the subsequent apoptosis of myeloma cells. Further analysis showed that BMP-2 induced down-regulation of Bcl-X(L) through the inactivation of STAT3, resulting in the induction of apoptosis in myeloma cells. We conclude that BMP-2 may have the potential to be one of the novel therapeutic agents for treatment in patients with multiple myeloma because of the beneficial effects on both myeloma cells and bone diseases. In this review, we summarize data concerning BMPs and BMP-2-induced apoptosis of myeloma cells including our own recent experimental data.
authors: Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
authors: Chiharu
authors: C
authors: Kawamura
authors: Masahiro
authors: M
authors: Kizaki
authors: Yasuo
authors: Y
authors: Ikeda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D017978:Receptors, Growth Factor / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors