Bone Morphogenetic Protein 9 Is a Potential Tumor Suppressor in Osteosarcoma

: Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. Although accumulating evidence has shown that BMP9 plays important roles in the regulation of various cellular processes, the function of BMP9 in clinical osteosarcoma remains to be explored. In this study, BMP9 expression was analyzed in 55 osteosarcoma patient samples and their matching, distant non-cancerous tissues. And the roles of BMP9 in osteosarcoma cell proliferation, apoptosis and cell cycle were also examined. Our results showed that different expression level of BMP9 was detected in all osteosarcoma samples while no expression in normal tissues. Surprisingly, there was a negative association between the expression level of BMP9 and osteosarcoma grade, with low level of BMP9 being found in high histological grade osteosarcoma. Knockdown of BMP9 accelerated the proliferation of MG63, SaOS-2, and U2OS cells. BMP9 overexpression, however, induced cell apoptosis in U2OS cells. Together, these results indicated that BMP9 plays a pivotal role in osteosarcoma. Future studies defining the mechanism of BMP9 effect may lead to novel therapeutic approaches for osteosarcoma.